Elements  ot  Stereochemistry 


THE 

Elements  of  Stereochemistry 


BY  A.  HANTZSCH 


Translated  from  the  last  Preneh  Edition  of 
Guye  and  Gantier 


BY  CHAKLES  G.  L.  WOLF 


EASTON,   r\. 

THE  CHEMICAL  FUBLIvSHIWi  COMPANY. 
1901. 


COPYRIGHT,  1901,  BY  EDWARD  HART 


AUTHOR'S  PREFACE. 


These  elements  of  stereochemistry  are  not  more  extensive 
than  the  stereochemistry  of  van  't  Hoff  and  Meyerhoffer,  re- 
cently published.  There  would  hence  scarcely  be  any  reason 
for  publishing  them  if  they  were  not  distinguished  by  a  dif- 
ferent rearrangement  of  the  contents,  and  particularly  in 
their  treatment  of  developments  of  the  stereochemistry  of 
nitrogen  compounds  and  of  inorganic  substances. 

The  first  part  is  devoted  to  the  study  of  molecular  asym- 
metry and  of  optical  isomerism.  These  questions  have  been 
treated  so  splendidly  by  the  founders  of  stereochemistry,  that 
they  scarcely  need  mention,  and  therefore  their  treatment  in 
this  book  has  been  somewhat  condensed.  Moreover,  the 
theoretical  conceptions  which  serve  As  a  basis  for  their  expla- 
nation are  no  longer  discussed;  hence  a  fuller  treatment  than 
has  been  given  in  these  elements  has  not  been  deemed  neces- 
sary. 

The  same  cannot  be  said  of  the  second  part,  which  is  de- 
voted to  geometric  isomerism  and  to  the  study  of  facts 
which  can  be  attributed  to  relative  distances  of  the  atoms  in 
the  molecule.  In  the  above-mentioned  classic  work,  these 
facts  are  treated  in  rather  a  summary  way..  Because  of  their 
increasing  importance  and  of  the  extension  of  this  new  chap- 
ter in  chemistry,  a  more  complete  explanation  of  these  de- 
velopments seems  justifiable.  With  regard  to  the  stereo- 
chemistry of  nitrogen  there  has  not  been,  up  to  the  present, 
any  complete  monograph  concerning  the  same.  This  has 
been  the  reason  for  treating  this  question  in  some  detail. 
Moreover,  in  consequence  of  the  scientific  discussions  of 
which  it  has  been  the  center,  it  seems  somewhat  advisable  to 
show  that,  as  a  matter  of  fact,  it  was  not  so  complicated  as 
it  would  appear  at  first  sight. 

Nevertheless  the  book  which  I  present  to  the  public  still 
preserves  the  character  of  a  "precis,"  as  the  time  is  not  yet 


iv  PREFACE 

at  hand  when  one  may  represent  a  complete  work  on  stereo- 
chemistry. In  order  to  preserve  this  sketchy  character  all 
details  and  all  bibliographic  references  which  were  not 
strictly  necessary  have  been  left  out.  I  wish  to  express  my 
thanks  to  Dr.  A.  Miolati  for  the  part  which  he  has  taken  in 
the  editing  of  a  chapter  of  this  book. 


ENGLISH  TRANSLATOR'S  PREFACE. 


The  translation  of  the  French  edition  of  Prof.  Hantzsch's 
' '  Gmndriss  der  Stereochemie, ' '  from  the  enlarged  French 
translation  of  Guye  and  Gautier,  was  undertaken  in  the  hope 
that  a  small  handbook  dealing  more  particularly  with  the 
important  stereochemistry  of  the  compounds  of  nitrogen, 
would  be  acceptable  to  English  readers.  This  translation 
has  been  made,  not  only  frpm  the  French  edition,  but  the 
original  German  work  has  also  been  freely  used,  and  the 
translator  has  had  the  advantage  of  the  personal  advice  of 
Prof.  Hantzsch,  to  whom  he  wishes  to  express  his  sincere 
thanks. 

CHEMICAL  LABORATORY, 
CORNELL  UNIVERSITY  MEDICAL  COLLEGE, 
NEW  YORK. 


CONTENTS 


INTRODUCTION 

Definition  i 

The  Development  of  Stereochemistry        -  3 

General  Characteristics  of  Stereochemical  Isomerism  5 


PART  I.     OPTICAL  ISOMERISM 

The  Stereochemistry  of  Compounds  Presenting 
Molecular  Asymmetry 

I.  Theory  of  Molecular  Asymmetry  or  of  the  Asymmetric  Car- 

bon Atom — Analogy  between  Crystalline  Asymmetry 

and  Molecular  Asymmetry  9 

Demonstration  based  on  isomerism  (Van't  Hoff)  11 

Demonstration  based  on  molecular  asymmetry  (Iye  Bel)        14 

II.  The    Consequences    of   the    Theory   of  an  Asymmetric 

Carbon  Atom,  and  their  Verification      -  20 

III.  Compounds  with  More  than  One  Asymmetric  Carbon 

Atom   -  26 

a.  Number  and  nature  of  isomers  27 

b.  Representation  of  optical  isomers — projection  formulae        31 

c.  Principal  examples  of  isomers  with  several  asymmetric 

carbon  atoms  34 

IV.  Formation  of  Asymmetric  Active  Compounds      -  38 

a.  Synthesis  of  racemic  compounds   from  symmetric  sub- 

stances .  38 

b.  Cleavage  of  inactive  mixtures  in  inactive  isomers  39 

a.  Cleavage  of  inactive  mixtures  by  means  of  living 

organisms  40 

|3.  Splitting  of  inactive  mixtures  by  means  of  active 

compounds  42 

y.  Spontaneous  separation  of  inactive  mixtures  by 
simple  crystallization  of  the  two  enantiomor- 
phous  isomers  43  • 


yi  CONTENTS 

V.  Transformation  of  Active  into  Inactive  Compounds          -        44 

a.  Without  change  of  configuration— Racemizatioii  44 

b.  Formation  of  inactive  compounds  starting  from  active 

compounds  by  the  influence  of  heat  and  with  change 
in  configuration  45 

VI.  Review  of  Compounds  Containing  Several  Asymmetric 

Carbon  Atoms       -  '  -        49 

a.  General  properties  of  these  compounds  49 

b.  Synthesis  of  compounds  containing  several  carbon  atoms    50 

c.  Molecular  transformations  of  active  compounds  with  sev- 

eral asymetric  carbon  atoms  55 

VII.  Determination  of  the  Configuration  of  Optical  Isomers        56 

Configuration  of  glucose,  mannose,  gulose,  and  fructose  61 

Configuration  of  the  glucoheptoses  64 

Configuration  of  the  mucic  and  talomucic  acids  65 
Configuration  of  dulcite,  galactose,  talose,  and  the  galactonic 

and  talonic  acids  68 

VIII.  Relation  between  Constitution  and  Rotatory  Power — 
Molecular  Asymmetry  7 1 

Compounds  with  several  asymmetric  carbon  atoms  ^78 

I.  Principle  of  the  independence  of  the  optical  effects 

of  asymmetric  carbon  atoms  79 

II.  Principle  of  algebraic  accumulation  79 
Polarimetric  observations                                                                    80 

Stereochemistry  of  the  Asymmetric  Compounds  of  Nitrogen        82 


PART  II.     GEOMETRICAL  ISOMERISM 

Stereochemistry  of  Unsaturated  and  Cyclic  Compounds,  and  the 

Compounds  of  Nitrogen 
General  Theory  of  Saturated  and  Unsaturated  Compounds        86 

I.  Stereochemistry  of  the  Unsaturated  Compounds  of  Carbon. 

Isomerism  in  the  Ethylene  Group  -        91 

a.  General  properties  91 
Principal  groups  of  geometrical  isomers                                   92 

b.  Determination  of  the  configuration  of  geometrical  unsatu- 

rated  isomers  94 

a.  By  relations  established  between  unsaturated  and 

cyclic  compounds  94 


CONTENTS  Vll 

ft.  By    relations    established    between    ethylene    and 

acetylene  derivatives  97 

•y.  By  relations  established  between  saturated  and  un- 

saturated  compounds  100 

rf.  By  relations  established    between    ethylene    deri- 
vatives 104 
Uncertainty  of  the  determination  of  configuration  107 

c.  Changes  in  configuration  of  geometrical  isomers  of  the 

ethylene  group  108 

a.  With  change  of  constitution  108 

/3.  Direct   transformation  without  change  of   consti- 
tution 108 

Transformation  of  geometrical  isomers  of  the  ethylene  series 

under  the  influence  of  heat  109 

Spontaneous  transformation  of  isomeric  ethylene  derivatives 

in  the  presence  of  certain  substances  in 

Difficulties  in  the  determination  of  configuration  in  the  case 

of  spontaneous  molecular  transformations  112 

Attempts  to  interpret  the  phenomena  of  molecular  transpo- 
sition 113 

Configuration  of  ethylene  compound  of  which  the  two  geo- 
metric isomers  are  not  known  117 

II.  Stereochemistry  of  Saturated  Compounds  -       118 

a .  Determination  of  the  position  of  advantage  or  of  unstable 

position  1 19 

b.  Configuration  of  cyclic  compounds  of  carbon  122 

III.  Stereochemistry  of  Cyclic  Compounds  125 

a.  General  125 

b.  The  geometrical  isomerism  of  the  polymethylene  deriva- 

tives 129 

c.  The  geometrical  isomerism  of   cyclic  compounds   with 

double  bonds  136 

d.  The  geometrical  isomerism  of  compounds  analogous  to 

polymethylene  derivatives  137 

IV.  The  Geometrical  Isomerism  of  Nitrogen  -       139 

Theoretical  139 

The    general    properties   of   the    geometrical    isomers    of 

nitrogen  141 

V.  The  Geometrical  Isomers  of  Carbon  and  Nitrogen      -  142 

a.  The  historical  proofs  of  identical  constitution  142 

b.  The  different  classes  of  stereoisomeric  oximes  145 

c.  Transformation  of  stereoisomers  into  one  another  153 

d.  Configuration  of  oximes  of  which  two  stereoisomers  have 

not  been  isolated  157 


yiii  CONTENTS 

VI.  Nitrogen    Compounds    Exhibiting    Geometrical    Isom- 

erism  -       I72 

1.  Stereoisomeric  diazo  compounds  •  i?2 

a.  Historical.    The  identity  of  the  structural  formulae  172 

b.  The  properties  and  methods  of  formation  of  the 

stereoisomeric  diazo  compounds  176 

c.  Determination  of  configuration  i?7 

d.  Reciprocal  transformation  of  stereoisomeric  diazo 

compounds  181 

e.  Configuration  of  diazo  compounds  of  which  there 

are  no  stereoisomers  181 

f.  Influence  of  constitution  on  configuration  182 

2.  Stereoisomeric  azo  compounds  183 


THE;  STEREOCHEMICAI,    ISOMERISM  OF  INORGANIC    COM- 
POUNDS.   BY  A.  WERNER  -  -  -  -  184 


Index  of  Subjects  -      201 

Index  of  Authors      -  -  205 


CORRECTIONS. 


Page  35,  last  formula, 


CH2 CH CH2  CH2 CH CH. 


for 


CH3C— CH3 


read 


CHSC— CHS 


H 


CH2 C C  <  CH2 C 

OH 


CH,  CH8 
Page  75,  line  15,  for  diaceyl  read  diacetyl. 
Page  in,  last  formula, 

CnH2— C— HM+I  C«H2,,+t— C— H 

for  read 

H— C— COOH  H— C— COOH 

Page  171,  footnote  2,  for  Paulz  read  Pauly. 


INTRODUCTION 

Stereochemistry,  as  the  name  indicates,  is  the  study  of 
the  relations  between  the  chemical  phenomena  of  com- 
pounds, and  the  arrangement  in  space  of  the  atoms  com- 
posing them.  One  terms  this  arrangement  of  atoms  in 
space  molecular  configuration,  or  more  simply,  configura- 
tion, and  one  defines  as  stereoisomers  those  compounds  of 
the  same  chemical  constitution  but  with  different  con- 
figuration. 

Stereochemistry  is  based  on  the  fundamental  assump- 
tion that  a  molecule  has  three  dimensions,  as  have  all 
bodies  in  nature.  Nevertheless  it  has  no  need  whatever 
of  any  precise  notion  of  affinity,  that  is  of  the  working 
of  atoms  one  on  the  other,  nor  of  numerical  relations 
which  govern  the  joining  of  one  element  to  another  or 
the  property  which  is  usually  designated  "valence." 
'It  rests  in  the  second  place  on  the  following  considera- 
tion which  is  a  result  of  isomerism  itself  ;  that  is,  the 
knowledge  that  the  atoms  in  a  molecule  cannot  be  in  a 
state  of  chaotic  confusion  but  must  within  certain  limits 
occupy  positions  of  stable  equilibrium. 

It  is  not  necessary  to  take  into  account  intramolecular 
atomic  movements,  although  their  existence  cannot  be 
doubted,  but,  because  by  reason  of  their  periodicity  one 
can  assume  that  the  atoms  occupy  a  certain  relatively 
fixed  position  to  one  another. 

Under  these  conditions  one  ought  to  assume  stereo- 
chemically  that  the  molecule  consists  of  a  stable  system 
of  material  points,  and  dynamics  should  be  taken  into 


2  ELEMENTS   OF  STEREOCHEMISTRY 

consideration  only  in  such  special  cases  as  molecular 
transpositions. 

According  to  le  Bel1  the  ground  work  of  stereochemistry 
ought  to  be  deduced  from  purely  mechanical  considera- 
tions independent  of  conceptions  regarding  valency  and 
structural  formulae,  simply  by  using  our  notions  of 
equilibrium  and  of  symmetry.  In  any  case  the  develop- 
ments of  this  theofy  are  independent  of  a  hypothesis 
which  is  apparently  not  true,  and  which  is  in  fact  contra- 
dicted by  certain  facts  which  consist  in  regarding  valence 
as  an  attractive  force  regulating  the  relative  positions  of 
atoms  to  one  another. 

Nevertheless  it  is  more  convenient  to  found  stereo- 
chemistry as  Van't  Hoff  has  done  by  using  constitutional 
formulae.  This  has  the  advantage  in  the  first  place  that 
it  lends  itself  easily  to  the  conception  of  the  student 
already  familiar  with  the  notation  currently  used  in 
chemistry,  and  in  the  second  place  that  stereochemistry  is 
born  of  constitutional  formulae.  L,et  us  admit  then,  for 
the  sake  of  simplicity  and  in  the  absence  of  negative 
indications,  that  the  valence  of  an  element  represents  not 
only  its  capacity  for  uniting  with  other  elements,  but  is 
the  resultant  of  forces  regulating  the  spatial  position  of 
that  element  with  others  ;  that  with  elements  other  than 
monovalent  these  forces  themselves  equal,  are  orientated 
in  space  in  definite  directions,  but  can  according  to  cir- 
cumstance be  changed  ;  and  lastly  in  the  case  of  unsat- 
urated  compounds  these  forces  or  linkings  can  be  double 
or  multiple. 

These  are  the  isomeric  phenomena  which  have  most 
contributed  to  show  the  necessity  of  stereochemical  con- 
ceptions. It  was  thought  in  the  beginning  that  consti- 

1  Revue.  Scientifique,  48,  609  (1891). 


DEVELOPMENT  OF  STEREOCHEMISTRY        3 

tutional  formulae  should  enable  one  to  take  into  considera- 
tion the  number  as  well  as  the  properties  of  all  isomeric 
compounds,  and  the  latter  should  conform  to  the  different 
modes  of  intra-atomic  linkage.  It  is  necessary  to  remem- 
ber that  facts  had  appeared  for  a  long  time  quite  in 
accordance  with  this  view.  Meanwhile  some  exceptions 
rare  at  first,  but  ever  increasing,  demonstrated  the  existence 
of  cases  of  isomerism  quite  unexplained  by  means  of 
constitutional  formulae. 

These  exceptions  were  classed  under  the  vague  term 
physical  isomers,  of  which  the  characteristics  were  never 
precisely  defined.  Constitutional  formulae  at  first  being 
constructed  in  a  plane,  the  natural  sequence  was  to 
explain  these  exceptional  cases  of  isomerism  as  due  to 
different  arrangement  of  the  atoms  in  space.  This  idea 
was  the  starting-point  of  stereochemistry. 

THE  DEVELOPMENT  OF  STEREOCHEMISTRY 

It  was  Pasteur1  who,  in  1860  andi86i,  founded  stereo- 
chemistry by  showing  the  remarkable  properties  which 
characterize  the  tartaric_  acids,  and  by  attributing  to 
molecules  certain  of  the  properties  of  crystals. 

Wislicenus2  in  1873  pronounced  constitutional  formulae 
as  then  known  insufficient,  notably  in  the  case  of  the 
lactic  acids,  and  proposed  that  one  should  substitute 
spatial  formulae. 

Shortly  after,  Van't  Hoff3  and  le  Bel4  quite  independ- 
ently of  one  another  developed  the  fundamental  theory 
of  the  asymmetric  carbon  atom,  and  of  its  application  to 
the  explanation  of  optically  active  compounds.  These 

1  Pasteur:  "R6cherches  sur  la  desymm£trie  mol£culaire  des produits  organ 
ique  naturels,"  Conf.  Soc.  Chim.  Paris  (1861). 

2  Ann.  Chem.  (I^iebig),  167,  343. 

3  Chi mie  dans  1'  6space  1873;  "Dixann6es  dans  1'histoire  d.  uneth£orie  1887.'' 

4  Bull. Soc.  Chim.  (2)  22,  337. 


4  ELEMENTS   OF   STEREOCHEMISTRY 

two  scientists  have  been  the  founders  of  modern  stereo- 
chemistry. Their  conceptions  are  very  nearly  the  same, 
the  differences  being  superficial. 

I,e  Bel  bases  his  theories  on  considerations  of  chemical 
mechanics,  while  Van't  Hoff  bases  his  on  the  considera- 
tion of  constitutional  formulae  as  ordinarily  employed. 
The  opinions  of  Van't  Hoff,  spread  in  Germany  by  the 
translation,  by  Hermann,  of  Van't  Hoff's  book  (1877), 
led  Baeyer1  to  explain  in  a  stereochemical  way  certain 
remarkable  properties  of  cyclic  compounds,  and  one  should 
mention  as  a  product  of  the  evolution  of  this  newer 
organic  chemistry  the  bringing  forward  of  the  prismatic 
formula  for  benzene  by  Ladenburg,  the  remarks  of 
Graebe  on  the  nature  and  formula  of  the  phthalic  acids, 
and  other  observations  of  different  authors. 

A  publication  by  Wislicenus2  constitutes  an  important 
advance  which  opened  the  way  to  experimental  work  of  a 
new  kind.  Since  then  the  stereochemistry  of  carbon  has 
been  studied  by  other  chemists,  notably  V.  Meyer, 
Friedel,  Bischoff,  and  particularly  by  Emil  Fischer 
whose  work  in  the  sugar  group  is  well  known. 

Recently  Guye  has  undertaken  the  study  of  these 
questions  from  a  mathematical  point  of  view,  while 
Werner  has  formed  the  basis  of  a  stereochemistry  of 
inorganic  compounds. 

Van't  Hoff  and  Wunderlich3  have  already  endeavored 
to  apply  stereochemical  methods  to  other  elements,  par- 
ticularly sulphur  and  nitrogen. 

The  ' '  stereochemistry  of  nitrogen  ' '  has  only  received 

1  Ber.  d.  chem.  Ges.,  18,  2277. 

2  Abhadg.    d.  mathem.    phys.    Classe  der    Sachs,  Akad.  Wissenschaften, 
V,  xiv. 

8  Die  Configuration  organischer  Molekule,  1886. 


STEREOCHEMICAI,   ISOMKRISM  5 

experimental  confirmation  since1  the  work  of  Hantzsch 
and  Werner2  and  of  le  Bel.5 

GENERAL  CHARACTERISTICS  OF  STEREOCHEMICAL 
ISOMERISM 

Stereochemical  isomers  identical  in  the  mode  of  union 
of  the  atoms,  one  to  another,  differ  only  in  the  geometri- 
cal relations  of  the  atoms  composing  the  compound.  It 
is  indeed  difficult  to  formulate  any  characteristic  dis- 
tinctions, but  one  may  say  that  usually  they  differ  from 
constitutional  isomers,  in  that  they  are  transformed  more 
easily,  one  into  the  other.  This  should  tend  to  prove  that 
the  geometrical  positions  of  atoms  in  a  molecule,  can  be 
much  more  easily  changed  than  the  respective  linking. 

Stereoisomers  may  be  included  in  two  classes : 

I.  Substances  identical  in  all  their  principal  properties, 
but  which  produce  different  effects  on  polarized  light,  in 
other  words,  which  are  characterized  by  difference  in  optical 
activity.  These  are  called  optical  isomers  or  enantio- 
morphous  isomers. 

In  these  compounds  one  can  regard  the  atoms  as  placed 
at  the  same  absolute  distance  from  one  another,  but  dis- 
posed in  a  different  order.  For  this  purpose  it  will,  per- 
haps, be  opportune  to  style  them  relative  Stereoisomers. 
We  shall  see  that  these  substances  are  characterized  by 
asymmetrical  atomic  groupings. 

Isomers  of  this  kind  which  contain  only  one  asymmetric 
group  are  identical  in  all  their  properties,  except  in  their 
action  on  polarized  light.  Those,  however,  which  con- 

1  V.  Meyer  and  Goldschmidt :  Ber.  d.   chem.   Ges.,   16,   2177  ;  Auwers  and 
Meyer  :  Ibid.,  21,  790  ;  Beckmann  :  Ibid.,  22,  429  ;  etc. 

2  Ibid.,  23,  i,  1243. 

3  Compt.  rend.',  112,  724. 


6  ELEMENTS   OF   STEREOCHEMISTRY 

tain   several   asymmetric  groups  may   not  only  differ  in 
their  physical,  but  also  in  their  chemical  properties. 

According  to  the  element  determining  the  asymmetry 
we  distinguish  : 

a.  Compounds  of  carbon   optically  active,  i.  e.,  those  in 
which  the  grouping  is  asymmetric  with  regard  to  the  atoms 
of  carbon. 

b.  Derivatives  of  nitrogen  optically  active,  i.  e. ,  those  in 
which  the  grouping  is  asymmetric  with  regard  to  the  atoms 
of  nitrogen. 

II.  Substances  which  without  action  on  polarized  light, 
and  in  spite  of  the  identity  of  their  constitutional  (plane} 
formulae,  and  the  characteristics  which  result  therefrom, 
present  differences  in  their  chemical  and  physical  behavior 
unexplainable  by  simple  formulae . 

These  substances  are  to  be  met  with  in  the  groups  of 
cyclic  compounds,  and  also  in  the  unsaturated  groups,  or 
in  those  containing  double  bonds.  For  lack  of  a  more 
precise  term  this  class  of  compounds  is  called  geometrical 
isomers.  In  the  case  of  these  isomers,  stereochemistry 
assumes  that  the  distance  between  the  atoms  is  different. 
In  order  to  distinguish,  one  might  call  substances  in  the 
first  class,  absolute  stereoisomers.  One  finds  bodies  of 
this  class  among  the  derivatives  of  carbon  and  of 
nitrogen.  We  may  subdivide  the  members  of  the  second 
class  under  the  following  four  heads  : 

a.  Compounds  characterized  by  one  or  more  double  bonds 
between  two  atoms  of  carbon.  These  are  true  geometrical 
isomers  of  carbon. 

ft.  Saturated  cyclic  compounds. 

y.   Compounds  characterized  by  one  or  more  double  bonds 


STEREOCHEMICAI,  ISOMERISM  7 

between  an  atom   of  carbon  and  an  atom  of  nitrogen,  or 
geometrical  isomers  of  carbon  and  nitrogen. 

6.   Compounds    characterized    by   double  bonds  between 
atoms  of  nitrogen  or  geometrical  isomers  of  nitrogen. 


PART  I.— OPTICAL  ISOMERISM 


THE    STEREOCHEMISTRY    OF    COMPOUNDS     PRE- 
SENTING MOLECULAR  ASYMMETRY 


I.  THEORY  OF  MOLECULAR  ASYMMETRY  OR  OF  THE 
ASYMMETRIC  CARBON  ATOM 


Analogy   between    Crystalline  Asymmetry  and  Molecular 
Asymmetry 

The  first  cases  of  isomerism  unexplained  by  ordinary 
plane  formulae,  were  observed  in  the  class  of  bodies 
grouped  in  Class  I.  These  substances,  alike  for  the  most 
part  in  their  properties,  are  distinguished  by  their  action 
on  polarized  light  whether  in  the  liquid  state  or  in  solution. 
From  their  turning  the  plain  of  polarized  light  to  the  left, 
or  to  the  right,  they  are  called  dextrorotatory  or  laevo- 
rotatory.  These  substances  can  be  compared  to  a  class 
of  mineral  compounds  which  have  been  known  for  a  long 
time,  the  crystalline  forms  of  which  are  active  and 
present  themselves  in  two  modifications,  left-  and  right- 
handed  crystals. 

But  there  is  a  fundamental  difference  between  these 
two  classes,  the  organic  and  the  mineral  isomers,  and  it 
is  above  all  concerned  with  the  disappearance  or  main- 
tenance of  these  differences  under  distinct  conditions. 

The  rotatory  power  of  inorganic  compounds  has  only 
been  observed  in  the  crystalline  state.  It  disappears  if 
the  substance  is  converted  into  the  amorphous  condition, 
as  in  the  case  of  melted  silica,  and  when  the  substance  is 


10  ELEMENTS   OF   STEREOCHEMISTRY 

brought  into  solution  as  in  the  case  of  sodium  chloride. 
It  depends  then  on  a  peculiarity  in  the  structure  of  the 
crystal  itself  since  it  disappears  when  the  crystalline  form 
is  destroyed. 

It  was  in  connection  with  quartz  that  enantiomor- 
phism  was  first  discovered  by  Biot  and  Pasteur.  The  dex- 
tro-  or  laevorotatory  individual  crystals  are  really  right- 
and  left-handed  ;  they  present  hemi-  or  tetrahedral  faces, 
non-superposable,  the  projection  of  which,  on  a  cylinder, 
gives  rise  to  a  spiral,  turning  either  to  the  left  or  to  the 
right.  Crystals,  otherwise  identical  in  form,  are  dissimilar, 
in  that  the  one  is  the  mirror  image  of  the  other.  The 
cause  of  this  rotatory  power1  results  from  the  disposition 
in  a  helix,  of  the  crystalline  elements  around  the  prin- 
cipal axis  of  the  crystal. 

The  molecules  themselves  are  inactive,  but  unite  at 
the  moment  of  crystallization  to  form  elements  of  an 
asymmetric  structure. 

We  know  that  if  we  arrange  a  number  of  layers  of 
mica,  one  above  the  other,  in  such  a  way  that  each  is 
turned  in  a  definite  direction  through  at  an  angle  of  60° 
to  the  member  next  lower,  that  we  obtain  an  artificially 
active  system  which  is  laevorotatory  when  the  lamellae 
are  superimposed  with  a  left-handed  turn,  and  vice  versa.2 
Optical  activity  in  this  case  depends  on  the  form  in  which 
the  material  is  arranged. 

It  is  quite  otherwise  with  the  optically  active  organic 
substances,  as  these  still  preserve  their  optical  properties 
in  solution,  and  even  in  the  gaseous  state,3  conditions 

1  Sohucke  :  Zeit  f.  Kryst.   und  Min.,   13,  229  ;  Mallard  :  Ann  d.  Mines,    19, 
256  (1881). 

2  Reusch  :  Pogg  Ann.,    138,  628  ;  Fresnel's  Works,  i,  460  and  505  ;  Verdet: 
Optique  Physique,  u,  201. 

8  Gernez:  Ann.  ijc.  Normal.  Sup.  I;  Guye  and  Do  Amaral  Arch.  sc.  ph.  nat. 
Geneve,  1895. 


OPTICAL,   ISOMERISM  II 

under    which    the  molecular    aggregation    is    certainly 
destroyed. 

The  cause  of  this  activity  then,  is  not  to  be  sought  in 
the  region  of  molecular  physics,  but  in  pure  chemistry 
itself  ;  it  should  reside  in  the  peculiar  arrangement  of  the 
atoms  in  the  molecule,  and  by  analogy  with  the  optically 
active  crystals,  it  should  be  attributed  to  a  sort  of 
molecular  enantiomorphism,  or  according  to  Pasteur,  to 
molecular  asymmetry.  Van't  Hoff  and  le  Bel  have  since 
shown  that  this  notion  of  molecular  asymmetry  can  be 
reconciled  with  structural  formulae,  and  that  at  once  one 
acquires  an  idea  which  permits  one  to  foretell,  with  per- 
fect exactness,  the  number  and  the  properties  of  optical 
isomers  as  well  as  other  unexpected  results  which  will  be 
developed  in  the  course  of  this  work.1 

Demonstration  based  on  isomerism  (Van't  Hoff).— 
Constitutional  formulae,  such  as  one  has  been  in  the 
habit  of  using,  are  insufficient  for  the  study  of  isomerism 
even  in  the  very  simplest  cases. 

If  one  considers  (according  to  the  principle  announced 
above)  that  the  four  valences  of  carbon  are  four  separate 
attractive  forces  acting  in  a  plane,  and  acting  at  right 
angles  to  one  another,  then  one  should  expect  in  the  class 
of  substances  having  the  general  formula,  C«2^2,  two 
isomeric  modifications 

b  b 

\  I 

a  —  C  —  a   and   a  —  C—  -b 


and  should  also  find  two  isomers  of  the  formula  Cafa  and 
three  in  the  case  of  £abcd.  No  known  facts  correspond 
to  the  existence  of  so  great  a  number  of  isomers. 

1  I<andolt's  "Drehungsvermogen,"  1879;  Friedel:  Rev.  gen.  des  Sci.,  4,  825. 


12  ELEMENTS   OF.  STEREOCHEMISTRY 

All  other  arrangements  of  the  valences  in  a  plane  sur- 
face lead  to  too  great  a  number  of  modifications.  It  is 
not  so,  however,  when  one  considers  these  valences  as 
having  a  position  in  space. 

As  a  matter  of  fact,  the  most  simple  way  in  which  to 
dispose  of  four  identical  bonds  connected  with  an  atom 
of  carbon,  consists  in  arranging  them  symmetrically  on  a 
spherical  surface,  in  which  the  carbon  atom  occupies  the 
center  of  the  sphere  ;  in  other  words  the  four  bonds 
should  be  situated  at  the  summits  of  a  regular  tetra- 
hedron of  which  the  carbon  atom  occupies  the  center. 

This  fundamental  hypothesis  can  be  put  forward  in  the 
following  way : 


The  four  valences  of  the  atom  of  carbon  are  directed 
towards  the  summits  of  a  regular  tetrahedron. 

As  a  result  of  this  proposition  the  compounds  C#2A,  and 
Ca2dc  cannot  give  isomers,  but  if  an  atom  of  carbon  is 
bound  to  four  different  groups,  one  can  conceive  of  two 
definite  stereoisomers  represented  by  figures  i  and  2. 

With  respect  to  the  group  a,  the  three  radicals,  d, 
c,  d,  are  orientated  in  the  inverse  way  in  two  figures.  The 
molecules  so  formed,  of  which  the  elements  are  the  same, 
and  which  only  differ  in  their  arrangement  in  space,  are 


OPTICAL   ISOMERISM  13 

not  superposable.  They  are  the  reflections,  one  of  the 
other,  in  a  mirror,  and  may  be  compared  to  the  right  hand 
placed  opposite  the  left. 

When  an  atom  of  carbon  is  in  this  way  bound  to  four 
different  groups  it  is  called  asymmetric. 

NOTE. — It  would  be  more  logical  to  say  that  an  asymmetric 
carbon  atom  is  an  atom  of  carbon  so  bound  that  it  no  longer  con- 
tains the  elements  of  symmetry.  This  is  evident  in  the  case  of 
the  compound  Cabcd  but  there  are  examples  of  compounds  such  as 
inosite  CHOH.  CHOH.  CHOH.  CHOH.  CHOH.  CHOH  which 


though  active  are  not  characterized  by  a  carbon  atom  united  to 
four  different  radicals.  In  this  case  the  activity  is  in  relation  with 
the  disappearance  of  the  elements  of  symmetry. — Guye  and 
Gauthier. 

The  two  isomers  corresponding  to  the  two  formulae 
given  above  are  called  optical  isomers  or  enantiomorphous 
compounds.  In  fact,  there  is  a  complete  analogy  between 
these  asymmetric  molecules  and  dissymmetric  crystals,  for 
in  both  cases  the  dissymmetry  is  the  cause  of  the  ro- 
tatory power, 

From  the  point  of  view  of  descriptive  geometry  one 
can,  in  the  same  way  as  in  the  case  of  hemihedral  crystals, 
produce  a  right-  or  left-handed  helix  passing  through  the 
four  summits,  and  corresponding  to  the  spiral  mentioned 
in  the  case  of  the  mica  plates,  as  well  as  to  the  crystals 
which  are  naturally  optically  active.  They  can  then 
represent  substances  of  equivalent  rotatory  power,  but 
with  opposite  signs  in  absolute  values. 

These  substances  are  besides  distinguished  when  they 
can  be  obtained  in  a  crystalline  state  by  true  enantiomor- 
phism,  but  as  a  result  of  complete  equality  of  the  inter- 
atomic distances  all  their  other  properties,  physical  as 
well  as  chemical,  are  absolutely  the  same. 


14  ELEMENTS   OF   STEREOCHEMISTRY 

The  particular  geometrical  form  of  each  tetrahedron 
has  not  been  taken  into  account  in  the  preceding  develop- 
ment of  this  theory.  It  is,  however,  quite  clear  that  the 
only  molecules  which  can  correspond  to  a  regular  tetra- 
hedron with  six  planes  of  symmetry  are  those  of  the 
simple  formula  C#4.  As  the  different  radicals  are  bound 
in  different  ways  to  the  carbon  atom,  and  as  they  attract 
also  by  reason  of  their  own  affinities,  it  is  probable  that 
the  form  of  these  tetrahedra  is  more  irregular  than  the 
different  radicals  themselves,  so  that  the  molecules  of  a 
compound  Qajbc  will  be  figured  as  tetrahedra  with  one 
plane  of  symmetry,  and  consequently,  asymmetric  mole~ 
cules  of  the  formulae  Qabcd  are  represented  by  molecules 
without  a  plane  of  symmetry,  or  by  asymmetric  figures 
of  which  one  can  construct  two  enantiomorphous  forms. 
Finally,  the  carbon  atom  itself  occupies  an  asymmetric 
position,  and  hence  justly,  may  be  called  the  asymmetric 
carbon  atom.  Actually  in  the  present  state  of  stereo- 
chemistry we  can  only  consider  as  yet  the  question  of  the 
mean  position  of  atoms  in  the  molecule,  and  general  no- 
tions of  symmetry.  One  can,  however,  speculate  on  the  rel- 
ative distances  between  the  atoms  and  neglect  provisionally 
the  precise  form  of  the  tetrahedra  in  each  given  case. 

Demonstration  based  on  molecular  asymmetry  ( Le  Bel ) . 
—This  proof1  at  first  sight  appears  somewhat  more  abstract 
than  that  of  Van't  Hoff  and  is  developed  quite  independ- 
ently of  any  hypothesis  regarding  valence. 

If  one  parts  with  the  notions  of  an  atom  and  of  a 
molecule,  notions  it  is  true  hypothetical,  but  generally 
accepted  by  reason  of  the  considerable  number  of  facts 
of  which  they  allow  interpretation,  one  can  conceive  the 
molecule  as  being  formed  in  two  distinct  ways. 

1  Conferences  Soci£t6  Chimique,  1889-92,  Paris,  1892. 


OPTICAL   ISOMERISM  15 

(1)  The   atoms  of   which   the  molecule  is  composed 
have  relatively,  the  one  to  the  other,  no  mean  fixed  posi- 
tion.    We    shall    designate    this    state     of   things     as 
' '  internally  ' '  unstable  or  chaotic. 

(2)  The  mean  centers  of  gravity  of  the  atoms  which 
form  the  molecule  are  fixed  relatively  the  one  to   the 
other,    a  state  which  in  contradistinction  we  may  term 
'internal  stability.'     Different  facts  allow  us  to  assume 
that  the  chemical  molecule  is  in  a  state  of  stability.     Be- 
sides, the  study  of  substitution  shows  that  certain  groups 
or  radicals  such  as  benzene  and  naphthalene,  are  trans- 
ported in  their  entirety  from  one  molecule  to  another, 
and    at    the   same  time    preserve  their  entity.     In  the 
same  way  in  the  aliphatic  series  a  certain  group,  such  as 
the  isopropyl,  remains  different  from  the  propyl,  and  the 
same  difference   is   observed  in  the  active  and  inactive 
amyl  compounds,  and  in  many  other  analogous  cases  also. 
These  facts  are  clearly  incompatible  with  a  theory  involv- 
ing a  chaotic  state. 

In  the  second  place,  isomerism  itself  is  a  proof  in  favor 
of  a  state  of  internal  stability.  We  recognize  numbers  of 
cases  of  isomeric  compounds,  such  as  ethyl  formate  and 
methyl  acetate  which  have  the  same  molecular  weight  in 
the  solid,  liquid,  and  gaseous  states  ;  but  nevertheless  these 
compounds  are  quite  distinct  in  their  chemical  and  physi- 
cal behavior.  For  a  long  time  this  has  been  attributed  to 
a  difference  of  arrangement  of  atoms  in  £he  molecule  and 
this  itself  implies  a  certain  internal  stability. 

(3)  We  can  explain   only   with  difficulty  how,   in  a 
molecule  in  which  the  atoms  were  in  a  state  of   chaos, 
optical  activity  could  be  produced.     We  know  that  all 
active   media  are   necessarily  dissymmetric,1  and  that  in 

1  Soret :  Trait6  de  Crystallographie,  p.  41  (1893). 


1 6  ELEMENTS   OF   STEREOCHEMISTRY 

compounds  which  display  this  property  in  the  solid,  dis- 
solved, and  gaseous  states,  this  activity  can  only  be 
attributed  to  asymmetry  taking  place  in  the  molecule 
itself.  It  cannot  result  from  asymmetric  aggregations 
of  molecules,  since  cryoscopic  measurements,  the  study  of 
vapor-densities,  and  the  method  of  Ramsay  and  Shields, 
have  shown  that  aggregations  of  this  sort  do  not,  as  a 
rule,  exist  in  active  compounds.  Dissymmetry  in  active 
molecules  cannot  be  conceived  in  a  chaotic  state  which 
presupposes  atomic  movements  which  are  absolutely 
irregular. 

This  necessary  relation  between  rotatory  power  and 
asymmetry  in  the  molecule  already  proposed  by  Biot, 
was  demonstrated  by  the  classic  researches  of  Pasteur. 
It  is,  as  with  the  principle  of  internal  stability,  at  the 
basis  of  stereochemistry  of  active  compounds.  The  idea 
of  an  active  compound,  on  the  other  hand,  is  nothing 
more  than  a  consequence  of  these  two  fundamental 
notions,  and  of  the  formulae  developed  in  the  course  of 
modern  chemistry. 

We  shall  now  come  back  to  a  characteristic  property 
of  these  formulae  ;  viz. ,  mobile  union.  In  the  formulae  as 
developed,  the  linking  between  two  atoms  of  carbon  is 
mobile. 

Let  one  take  as  an  example,  ethane,  CH3.CH3,  and 
admit  for  an  instant  that  absolute  rigidity  of  the 
molecule  takes  place.  Then  the  six  atoms  of  hydrogen 
form  two  equilateral  triangles  parallel  to  one  another, 
and  in  arranging  in  the  most  simple  way,  we  have  a 
prismatic  figure,  analogous  to  Ladenburg's  prism 
formula  for  benzene  : 


OPTICAL   ISOMERISM 


H 


H 


X 

y 

As  a  consequence  we  should  find  three  trichlor  deriva- 
tives. But  experimental  evidence  leads  to  two  only  ; 
viz. ,  ethylene  chlorid  and  ethylidene  chlorid.  Further, 
the  synthetic  reactions  and  the  properties  of  these  com- 
pounds show  clearly  that  in  the  one  case  the  two  chlorin 
atoms  are  bound  each  to  one  carbon  atom,  while  in  the 
other,  the  two  are  united  to  the  same  carbon  atom.  As 
the  most  simple  hypothesis  which  conceives  of  molecular 
rigidity  furnishes  us  with  more  isomers  than  experience 
has  shown,  we  must  reject  hypotheses  which  suggest  rigid 
structures  in  cases  which  are  more  complicated. 

The  results  of  the  consideration  of  this  example,  and 
of  the  consideration  of  a  large  number  of  analogous  cases 
in  which  a  series  of  isomers  should  exist,  were  there  a 
rigid  system,  have  failed  completely  to  demonstrate  that 
rotation  does  not  take  place.  We  must  then  conclude 
that  radicals  united  by  a  single  linking,  are  not  fixed  in  an 
unalterable  manner,  or  what  comes  to  the  same  thing, 
that  if  fixed,  they  are  held  feebly,  and  this  rigidity  is  ren- 
dered nil  by  the  concussions  of  successive  molecular  shocks. 

Finally,  from  the  moment  that  we  conclude  that  this 
orientation  is  not  permanent,  and  that  it  is  not  able  to  be 
the  cause  of  isomeric  chemical  compounds,  we  are  led  to 
assume  that  it  is  insufficient  to  produce  optical  isomerism, 
for  this  implies  molecular  asymmetry. 


1 8  \     ELEMENTS   OF  STEREOCHEMISTRY 

First  Law. — Asymmetric  Atoms 
Let  us    consider    a  given  molecule  with   a  power  of 
rotation,  containing   an   atom  A  (carbon   or   nitrogen), 
bound  to  several  monovalent  atoms  or  radicals,  R,   R,'  R". 
These  radicals  being  united  to  A  by  mobile  linking,  their 
orientation  can  play  no  part,  and  they    themselves   will 
not  be  capable  of  producing  asymmetry  ;  in  a  word,  they 
act  as  if  all  their  respective  forces  were  concentrated  on 
a  point.     Then  the  asymmetry  which  necessarily  exists 
in  the  molecule  (for  we  have  assumed  it  to  be  active), 
cannot  result  from  the  permanent  asymmetric  disposition 
of  the  radicals,  R,  R',  R",  around  A,  or  from  an  asymmetry 
existing  in  one  of  the  radicals,  R,  for  example,  since  this 
radical  can  be  decomposed  into  its  constituent  groups  to 
which  we   can   apply  the  same  reasoning.     There  must 
;   be  then  in  one  of  these  groups  a  polyvalent  atom  around 
/    which  the  radicals  affect  an  asymmetric  disposition,  a 
condition  which  can  only  be  fulfilled  if  they  be  not  in  the 
same  plane.     This  atom  will  be  called  in  future  "  asym- 
\  metric." 

Such  is  the  fundamental  law  of  the  asymmetric  carbon 
or  nitrogen  atom,  which  is  demonstrated  by  the  con- 
sideration of  mobile  union  alone  (a  fact  based  on  purely 
experimental  grounds),  and  which  does  npt  compel  us  to 
consider  the  nature  of  the  forces  which  maintain  equi- 
librium in  the  molecule.  If  we  examine  this  question 
somewhat  more  closely,  we  shall  see  that  the  asymmetry 
due  to  the  arrangement  of  these  four  or  five  radicals  can 
be  produced  in  two  ways  only  : 

(i)  By  their  occupying,  or  not,  different  positions, 
these  radicals  are  distinguished  by  their  chemical  deport- 
ment. 


OPTICAL   ISOMERISM  19 

\      (2)  Certain  of  the  radicals  are  identical,  but  are  dis- 
\  tinguished  by  a  peculiarity  of  orientation. 

Facts  correspond  completely  to  the  first  condition,  for 
as  yet  we  know  of  no  simple  active  compound  with  two 
identical  radicals  united  to  the  atom  which  is  in  question, 
that  we  are  thus  led  to  the  second  law. 


Second  Law.  —  The  rotatory  power  disappears  when  two 
of  the  radicals  united  to  the  polyvalent  atom  become  identical. 

We  have  here  an  experimental  truth  to  which  there  is 
no  exception.  An  active  compound  becomes,  in  all  cases, 
inactive  when  two  of  the  atoms  or  radicals  united  to  the 
carbon  or  nitrogen  atom  become  similar,  and  cannot  be 
split  up  by  any  known  means  into  isomers  having  dextro- 
and  laevo-rotatory  power.  We  are  thus  led  to  specialize 
the  first  law.  An  active  compound  possesses  necessarily, 
a  carbon  or  nitrogen  atom  united  to  atoms  or  radicals, 
all  different  among  themselves.  As  this  concerns  more 
particularly  the  carbon  atom  we  are  naturally  led  to  the 
tetrahedral  formula. 

In  fact,  three  of  the  radicals  are  situated  in  a  plane, 
the  three  determining  the  plane,  and  the  fourth,  neces- 
sarily outside  the  plane,  forms  with  the  first  three,  a  tetra- 
hedron. This  tetrahedron  will  be  more  or  less  changed 
in  form,  according  to  the  substitutions  which  take  place 
in  the  molecule,  but  by  reason  of  the  internal  stability  of 
the  molecule  the  tetrahedral  shape  will  still  persist. 

It  should  be  here  remarked  that  for  compounds  of  the 
formula  C«4  the  tetrahedral  plan  is  not  necessarily  regular 
if  one  takes  away  the  notion  -of  valence.  In  this  case  the 
equilibrium  of  the  molecule  C<24  is  the  resultant  of  the 
attractive  or  repulsive  forces  between  each  of  the  atoms 
a  and  the  atom  C,  and  between  the  atoms  a  themselves  on 
the  other  hand.  According  to  the  intensity  of  these 


20  ELEMENTS  OF  STEREOCHEMISTRY 

attractions  or  repulsions,  we  can  conceive  that  the  atoms 
a  can  group  themselves  in  such  a  way  as  to  form  a 
symmetrical  tetrahedron,  but  different  at  the  same  time 
from  a  regular  tetrahedron.  These  conditions  appear  to- 
be  realized  in  the  case  of  certain  compounds  of  the 
formula  C«4  such  as  carbon  tetraiodid,  CI4,  which  does  not 
crystallize  in  the  cubic  system,  which  ought  to  be  the 
case  did  the  molecule  possess  really  a  cubical  symmetry 
corresponding  to  a  regular  tetrahedron.  It  must,  how- 
ever, be  said  that  the  observed  crystalline  forms  are  very 
near  in  symmetry  to  the  cube,  so  that  if  the  tetrahedron 
be  not  regular,  -it  differs  only  in  a  very  slight  degree  from 
that  form. 

II.  THE  CONSEQUENCES  OF  THE  THEORY  OF  AN  ASYM- 
METRIC CARBON  ATOM,  AND  THEIR  VERI- 
FICATION 

This  theory  is  now  based  on  so  large  a  number  of  facts-  • 
that  it  will  suffice  to  mention  some  of  the  more  striking 
examples. 

a.  All  active  compounds  contain  at  least  one  asymmetric 
carbon  atom. 

Example:  Lactic  acid,  CH3.CH(OH).COOH 

Malic  acid,  COOH.CHOH.CH2.COOH 
Asparagin,  COOH.CH(NH2).CH2NH2 
Leucin,  C4H9.CH(NH2).COOH 
Phenylglycollic  acid,  C6H5.CHOH.COOH 
Amyl  alcohol,  (C2H5).CH3.CH.CHaOH 
Ethyl  amyl,  CH3(C2H5).CH.C3H7 
Tyrosin,  C6H4OH.CH2.CH(NH2).COOH 
Tartaric  acid,  COOH.CHOH.CHOH.COOH 
Mannite,  CH2OH.(CHOH)4.CH2OH 
Saccharic  acid,  COOH.(CHOH)4.COOH 
Glucose,  CH2OH(CHOH)4.CHO 

1  I,e  Bel  :  Bull.  Soc.  Chim.  (3),  3,  788. 


OPTICAL,   ISOMERISM 


21 


Besides  these  may  be  mentioned  levulose,  dextrin,  and 
the  greater  number  of  the  carbohydrates,  turpentine  and 
its  derivatives,  camphor,  borneol,  menthol,  conicin, 
quinin,  and  many  of  the  alkaloids,  the  glucosides  and 
the  class  of  albuminoids. 

In  many  compounds  the  asymmetric  carbon  atom  is  to 
be  found  in  a  closed  chain  ;  e.  g. , 


H2C 
H2C 


/CH<\ 


\ 


CH2 
CH(C3H7) 


H 

Conicin. 


Camphor  according  to  the  formula  adopted, 


CH3 


v-3ii7^-i±           ^ 

/\ 

H2C        CH2 

HC       CO 
%/          C 

C 
CH3 

Kekul£ 

n2            v 

CH3—  C 

TT             f 

:—  CHS 

N           r 

C 
Bi 

•H3 

edt' 

CH,   CH, 


H2C 

I         I 
H2C       CO     CHCH3 


CH 

Bouveault3 


and  propylene  oxid, 


CH3  — CH  — CH2. 


1  I^adenburg  :  Ber.  d.  chem.  Ges.,  19,  2578,  2584. 

2  Ibid.,  26,  3047. 

3  Bull.  Soc.  Chim.  (3),  7,  531. 


22  ELEMENTS   OF   STEREOCHEMISTRY 

b.  There  are  no  active  compounds  without  an  asymmetric 
carbon  atom. 

This  fact,  although  at  first  contested,  is  now  firmly 
established. 

Some  substances  without  an  asymmetric  carbon  atom, 
such  as  propyl  alcohol,  CH3.CH2.CH2.OH,  styrol, 
C6H5.CH:CH2,  /?-picolin,  etc.,  were  first  considered 
active.  It  is  now  placed  beyond  a  doubt  that  these  sub- 
stances in  a  state  of  purity  are  inactive.  The  activity 
was  due  to  traces  of  active  compounds.  In  the  case  of 
propyl  alcohol,  it  was  due  to  an  admixture  of  active 
amyl  alcohol,  in  the  case  of  styrol  to  active  principles 
which  accompanied  it  in  storax. 

C.  The  optical  activity  disappears  when  the  asymmetric 
carbon  atom  becomes  symmetrical. 

This  is  the  case  when  the  molecules  Cabcd  are  trans- 
formed into  CabC2.  If  the  transformation  does  not 
destroy  the  asymmetry,  the  activity  persists. 

Active  amyl  alcohol  has  the  formula 
CH3  H 

\/ 

C 

C2H5          CH2OH 

We  already  know  more  than  forty  derivatives :  esters, 
halogen  substitution  products,  amins,  mercaptans,  valeric 
acid,  the  aldehyde,  etc.,  having  the  general  formulae 
CH3  H  CH3  H 

C  and  C 

/   \  /  \ 

C2H5  CH2X  C2H5  COOR       V 

All  these  compounds  are  active.1 

1  Guj'e:  Ann.  chim.  phys.  (6),  35,  145. 


OPTICAL   ISOMKRISM  23 

When  the  carbon  atom  remains  asymmetric  but  the 
optical  activity  is  lost  the  compound  is  called  racemic. 

On  the  other  hand  all  the  derivatives  which  have  lost 
their  asymmetric  structure  are  inactive  ;  e.  g. , 

CH3  H  CH3  H 

\   /  \   / 

C  C 

/   \  /  \ 

C2H5  CH3  C2H5  CH2.CH3 

Dimethyl  ethyl  methane.        Diethyl  methyl  methane. 

CH\ 

C:CH2 

C2H5 

Amylene. 

This  fact  is  also  confirmed  by  the  optical  properties  of 
the  products  of  fermentation,  so  that,  as  we  shall  see 
further  on,  the  compounds  produced  under  these  condi- 
tions are  generally  active  when  they  contain  an  asym- 
metric carbon  atom  and  are  always  inactive  when  they 
are  of  symmetrical  structure.  An  example  of  the  latter 
is  the  formation  of  succinic  acid  which  is  inactive  from 
the  following  active  compounds :  the  lactic,  tartaric, 
malic,  and  aspartic  acids,  and  starch. 

d.  All  active  compounds  exist  in  two  modifications  which 
are  identical  except  in  their  having  opposite  rotatory  power. 

We  have  already  had  occasion  to  mention  this  natural 
sequence  of  the  theory  in  speaking  of  optical  isomerism. 

We  may  take  for  examples  the  /-  and  ^-tartaric  acids, 
/-  and  ^-malic  acids,  /-  and  ^/-asparagins,  /-  and  ^-phenyl 
gly collie  acids,  the  /-  and  afconicins,  /-  and  ^/-glyceric 
acids,  and  many  others. 


24  ELEMENTS   OP   STEREOCHEMISTRY 

The  only  exceptions  to  this  rule  are  substances  with 
complex  formulae  of  which  we  know  as  yet  but  one 
modification.  The  converse  of  propositions  a  and  b,  viz., 
that  all  compounds  containing  an  asymmetric  carbon 
atom  must  be  active,  conform  neither  to  the  theory  or  to 
the  facts  adduced.  On  the  contrary  there  exists  a  large 
number  of  compounds  containing  an  asymmetric  carbon 
atom,  which  are  without  action  on  polarized  light. 

e.  Inactive  compounds  with  one  asymmetric  carbon  atom 
are  mixtures  or  equimolecular  compounds  of  the  laevo-  and 
dextro  rotatory  isomers. 

As  proof  of  this  may  be  cited  the  fact  that  a  great 
number  of  inactive  compounds  containing  a  single  asym- 
metric carbon  atom  have  been  split  up  into  their  respect- 
ive isomers  by  methods  which  will  be  given  further  on, 
while  at  the  same  time  these  same  methods  have  not 
allowed  us  to  isolate  any  active  compound  which  does  not 
contain  an  asymmetric  carbon  atom.  As  a  reciprocal  of 
the  law  formulated  under  c,  one  might  expect  that  the 
rotatory  power  of  a  compound  is  transmitted  to  all  its 
derivatives  so  long  as  the  carbon  remains  asymmetric. 
This  rule  is  not  without  exception,  for  although  the 
salts,  the  esters,  and  amidsof  the  active  lactic,  maliCi 
valeric,  and  phenylgly collie  acids  are  active,  the  halogen 
acids  derived  from  them,  i.  e.,  the  tf-brompropionic  acid, 
CH3.CHBr.COOH,  dibromsuccinic  acid,  COOH.CHBr.- 

CH3  Br 

fCHBr.COOH,  bromovaleric  acid,  C  and 

/   \ 

C2H5  COOH 

phenylbromacetic  acid,  C6H5.CHBr.COOH,  although 
dissymmetric  are,  known  only  in  an  inactive  modifi- 
cation. One  is  thus  led  to  ask  if  the  simple  difference 


OPTICAL    ISOMERISM  25 

in  the  four  radicals  saturating  the  valences  of  the 
carbon  atom  suffice  to  produce  the  power  of  rotation,  or 
whether  this  does  not  depend  also  on  other  factors,  e.g., 
the  nature  of  the  radicals  themselves. 

A  short  time  since,  experimental  evidence  was  lacking 
on  this  point  but  to-day  numerous  examples  prove  that 
the  smallest  difference  between  the  four  radicals  or  even 
the  replacement  of  a  halogen  by  a  hydrogen  suffices  to 
bring  out  again  the  rotatory  power. 

Secondary  amyl  iodid,  CH3.CHI.C3H7,  is  active  (leBel) 
and  so  is  the  crystallized  hexachlorohexane1  made  from 
mannite,  CH,OH.(CHOH)4.CH2OH,  monochlorsuccinic 
acid,  COOH.CHC1.CH2.COOH,  obtained  in  an  active  state 
by  Walden2  by  the  action  of  phosphorus  pentachloride 
on  malic  acid,  while  the  acid  obtained  by  Kekule3  by  the 
action  of  hydrobromic  acid  on  malic  acid  is  inactive. 
In  this  case  it  is  certain  that  we  are  dealing  with 
the  racemic  form.  The  many  chlorhydrins  and  brom- 
hydrins  obtained  from  propylglycol,  and  the  secondary 
alcohols,  butanol,  pentanol,  hexanol,  and  heptanol,  and 
from  the  ethyl  tartrates  and  lactates  are  also  inactive.4 
Recently  Walden  has  multiplied  these  examples  and  has 
definitely  demonstrated  that  the  simple  difference  between 
the  four  radicals  united  to  the  carbon  atom  suffices  to 
produce  optical  activity.5  If  the  active  compounds  do 
not  always,  give  asymmetric  active  derivatives  it  is 
because  certain  reactions  favor  the  formation  of  inactive 
mixtures  (vide  chapter  on  Phenomena  of  Racemization). 

1  Mourques :  Compt.  rend.,  in,  112. 

2  Ber.  d.  chem.  Ges.,  26,  210. 

3  Ann.  Chem.  (lyiebig),  130,  21. 

4  I,e  Bel :  Bull.  Soc.  China.,  (3),  9,  674. 
&  Ber.  d.  chem.  Ges.,  1895. 


26 


ELEMENTS   OF   STEREOCHEMISTRY 


III.  COMPOUNDS  WITH  MORE  THAN  ONE  ASYMMETRIC 
CARBON  ATOM 

The  preceding  developments  of  the  theory  have  been 
concerned,  strictly  speaking,  with  compounds  character- 
ized by  one  asymmetric  carbon  atom,  but  they  can  be 
applied  also  to  compounds  containing  an  unlimited 
number  of  asymmetric  groups,  on  condition  that  one 
takes  into  account  certain  complications  which  modify 
the  properties  of  optical  isomers,  and  also  their  number. 
It  is  better  at  first  to  meet  an  objection  which  strikes 
one  naturally  in  considering  the  subject.  These  com- 
pounds consisting  of  two  or  more  carbon  atoms  singly 
linked  ought  to  be  represented  by  two  tetrahedra  joined 
by  their  summits,  and  thus  for  ethane  we  should  have 
the  following  : 


Certain  derivatives  ought,  it  would  seem,  to  lead  to 
different  stereochemical  isomers  according  to  the  distance 
separating  the  respective  substituting  atoms. 

Thus,  for  ethylene  chlorid,  CH2C1— CH2C1,  one  can 
conceive,  at  least,  of  two  isomeric  forms  (Fig.  4)  which 
can  be  regarded  as  derived  one  from  the  other  by  a 
rotation  of  one  of  the  tetrahedra  around  the  common 


axis. 


It  should  be  the  same  in  the  case  of  compounds  con- 
taining several  asymmetric  carbon  atoms,   such  as  the 


OPTICAL   ISOMERISM  27 

compound  Cabc.Cdef .  As  cases  of  this  kind  have  never 
been  observed,  we  are  not  able  to  take  them  into  account  in 
the  study  of  substances  containing  more  than  one  asym- 
metric carbon  atom,  and  we  shall  assume  that  the 
rotatory  power,  and  the  number  of  isomers  depends 
exclusively  on  the  number  of  asymmetric  atoms  and  their 
-f  or  —  character.  In  this  way,  one  will  be  able  to 
treat  the  study  of  optical  isomers  independently  of  the 
principles  involving  a  mobile  union  and  of  a  special 
configuration  to  which  we  shall  return  later. 

a.  Number  and  nature  of  isomers. — Substances  con- 
taining one  asymmetric  carbon  atom  exist,  as  we  have 
seen  in  two  optically  active  modifications  which  can  be 
represented  by  -f-  A  and  —  A,  if  one  designates  by  A 
the  rotatory  power  of  the  asymmetric  group. 

Compounds  with  two  asymmetric  carbon  atoms  of  the 
general  formula  Cabc.Cdef  are  active  by  reason  of  an 
active  group  A,  and  also  by  reason  of  another,  B,  both 
of  which  can  exist  in  two  active  modifications.  This 
gives  thus  four  optical  isomers  : 

i.  -f  A  2.  -f  A  3.  --  A  4.  —A 

+  B  -B  +B  -B 

i  and  4  have  the  same  rotatory  power,  but  of  opposite 
sign,  and  this  is  the  same  with  2  and  3.  They  are,  in 
fact,  true  enantiomorphous  isomers.  This  explains  why 
i  and  4,  and  2  and  3  can  give  rise  to  compounds  or  to 
equimolecular  mixtures  which  are  inactive,  while  i  or  4 
mixed  in  the  same  proportion  with  2  or  3  give  active 
mixtures. 

Compounds  with  three  asymmetric  carbon  atoms  of  the 
formula  Cabc — Cde — Cfgh  contain  three  active 
groups,  A,  B,  and  C.  There  are  then  23  —  8  isomers 


28 


ELEMENTS   OF   STEREOCHEMISTRY 


i.  +  A 

2.     -f  A 

3-   +A 

4-   +A 

+    "D 
J) 

+  B 

-  B 

—  B 

-1-  C 

-C 

+  C 

—  C 

5-  -A 

6             A 
•                     -iJL 

7.   -A 

8.   -  A 

-h  B 

+  B 

—  B 

—  B 

+  c 

-C 

-f  c 

-  C 

Among  these  modifications  the  compounds,  i  and  8,  2 
and  7,  3  and  6,  4  and  5,  represent  substances  with  equal 
rotatory  power,  but  with  opposite  signs.  These  will 
then  form  four  racemic  compounds. 

Substances  containing  four  asymmetric  carbon  atoms 
of  the  formula  Cabe— Cde— Cfg1— Chik  will  give  as 
in  the  preceding  cases  24  =  16  isomers.  The  following 
table  enumerates  these  isomers.  Those  placed  one  above 
the  other  differ  only  by  the  characteristic  signs  of  the 
symbols,  A,  B,  C,  D. 


ii 


12 


16 


+ 
+ 
+ 
+ 
I 


[                       1                        1                        I                        1                    A 

+         +         +                                 +  '  B 

+                                        1                                   p 
v~ 

—1—                                                                          Ti 
i"                                                                 —      ^ 

+ 

-f                                           —    A 
i                             -<D 

1                                           JD 

I   '              |                                                    i         p 
v^ 

+      -f      +      +      —  r> 

' 


6         7 


8 


10 


To  formulate  a   general  law,  compounds  containing  n 
different  asymmetric  carbon  atoms  should  exist  to  the 

2* 
number  of  2"  forming  —  pairs  of  bodies  of  equal  rotatory 

power,  but  of  opposite  signs. 


OPTICAL   ISOMKRISM  29 

Number  of  optical  isomers  in  the  case  of  compounds  with 
symmetric  formulae, 

When  the  structural  formula  of  a  substance  with  several 
asymmetric  carbon  atoms  is  itself  symmetrical,  the  number 
of  optical  isomers  is  less  than  in  the  preceding  cases. 
Compounds  with  two  identical  asymmetric  carbon  atoms, 
Cabe — Cabc,  are  characterized  by  two  groups  — Cabc  with 
rotatory  powers  absolutely  equal.  Then  A  should  equal 
B,  and  the  configurations  2  and  3,  among  the  four 
mentioned  in  speaking  of  two  asymmetric  carbon  atoms, 
becoming  identical,  one  should  find  but  three  isomers  of 
which  the  rotatory  power  can  be  expressed  in  the  follow- 
ing way  : 

+  A  +  A-  —  A      . 

(l).  =  2A.     (2).  =0       (3).  -2A 

+  A  —A  -A 

Two  of  the  isomers,  i  and  3,  are  active  enantio- 
morphous  modifications  ;  2  is  inactive  in  spite  of  the  fact 
of  its  having  two  asymmetric  carbon  atoms  for  the  optical 
effect  of  the  -f  A  is  compensated  by  that  of  — A,  and  in 
this  manner  the  rotatory  power  is  reduced  to  zero. 

The  inactivity  of  this  kind  of  isomer  is  such  that  one 
is  not  able  to  split  it  into  two  optically  active  compounds. 
It  is  here  that  the  difference  lies  between  equimolecular 
mixtures  or  racemic  compounds  formed  by  the  union  of 
two  molecules,  right  and  left,  and  the  non-racemic  in- 
active compounds  which  are  only  found  in  the  case  of 
compounds  containing  two  or  more  asymmetric  carbon 
atoms.  This  point  cannot  be  too  strongly  emphasized, 
for  at  one  time  the  existence  of  an  inactive  non-racemic 
malic  acid,  COOH.CH2.CHOH.COOH,  was  in  doubt,  the 
existence  of  which  would  have  been  in  direct  opposition 
to  the  theory  of  van't  Hoff  and  le  Bel.  This  fact  has 


30  ELEMENTS   OF   STEREOCHEMISTRY 

been  put  beyond  question  by  the  researches  of  Bremer,1 
Anschutz,2  andj.  H.  van't  Hoff.3  The  same  reasoning 
can  be  applied  to  compounds  having  two  asymmetric 
carbon  atoms  indirectly  bound;  e.g.  ,Cabe — (Cd2)* — CabC. 
Compounds  with  three  asymmetric  carbon  atoms  of 
the  type  CabC — Cde — CabC,  although  apparently  sym- 
metrical, are  not  so  by  reason  of  the  relation  which  the 
central  groups  holds  to  the  other  two,  we  may  use  the 
same  figures  as  those  employed  on  page  26. 


A 
B 

C 

A 
B 

C 


i.     -r-     2.     +     3.     +     4. 


6.  7.     —     8. 

4-  4-  -          - 


4-  -  4-  - 

Now  A  =  C,  then  2  and  5  should  be  identical.  Besides 
i  =  3  for  with  these  two  isomers  the  central  carbon  atom 
becomes  symmetrical,  two  of  its  valences  being  saturated 
by  radicals  optically  identical.  (The  identity  of  i  and  3 
is  more  easily  seen  by  the  use  of  models. )  One  will  have 
in  the  same  way  6  =  8.  Altogether  there  remain  but 
4  isomers,  which  are  : 

A        +        4-        4- 

B          o  4-6 

Among  these,  the  first  and  last  are  optical  antipodes, 
while  the  other  two,  which  are  two  figures  non-super- 
posable,  and  each  having  one  plane  of  symmetry,  are 
the  non-racemic  inactive  compounds. 

For  substances  with  symmetrical  structure  with  four 
asymmetric  carbon  atoms,  CabC — Cde — Cde — CabC,  the 

1  Rec.  Trav.  Pays-Bas,  4,  180. 

2  Ber.  d.  chem.  Ges.,  18,  2713. 
8  Ibid.,  18,  2170. 


+f* 

-  fv*U*  -      *f~~ 

OPTICAL,   ISOMERISM  31 

isomers  are  ten  in  number,  for  in  making  A  =  D  in  the 
formulae  given  in  the  table  on  page  28,  the  compounds 
numbered  5-10  become  identical  with  those  numbered 
11-16,  and  in  this  way  the  1  6  modifications  are  reduced 
to  10.  Among  these  10  isomers,  7  and  8  are  inactive, 
through  intramolecular  compensation,  and  are  not 
racemic,  while  the  modifications,  i  and  4,  2  and  3,  5  and 
9,  6  and  10,  represent  enantiomorphous  compounds,  and 
hence  can  form  four  inactive  compounds  by  equimolecular 
mixture,  which  compounds  are,  however,  cleavable  into 
their  optical  constituents. 

A  careful  analysis  of  cases  permits  the  conclusion  that 
compounds  with  n  asymmetric  carbon  atoms,  of  which 
the  structural  'formula  is  symmetrical,  can  give  rise  to  N' 

isomers,  N  being  equal  to  2^~'/2  *  -j-  i     when  n  is  an 


even  number,  and  to  2n~l  when  n  is  uneven.1 

b.  Representation  of  optical  isomers.  Projection  form- 
ulae. —  Different  methods  of  representation  have  been  pro- 
posed to  bring  out  clearly  the  configuration  of  optical 
isomers.  Models  are  often  made  use  of  among  which 
those  described  by  Friedlaender2are  the  simplest.  They 
consist  of  small  spheres  to  which  are  attached  four  pieces 
of  India  rubber  tubing  pointing  in  the  direction  of  the 
four  summits  of  a  tetrahedron. 

These  four  tubes  represent  the  valences  of  a  carbon 
atom,  and  to  them  can  be  attached  -other  spheres  of 
various  colors  to  represent  the  different  groups.  These 
models  allow  one  to  grasp  mentally  the  most  complex 
cases  of  isomerism  in  an  easy  manner. 

It  is  more  difficult  to  represent  on  paper  the  configu- 

1  Fischer  :  Ber.  d.  chem.  Ges.,  24,  1839  ;  27,  3208. 

2  Ibid.,  24,  1339;  27»  32oS- 


ELEMENTS   OF   STEREOCHEMISTRY 


ration  of  the  different  isomers,  for  one  must  constantly 
keep  in  view  the  relations  which  the  changing  of  certain 
groups  to  the  right  or  to  the  left  involves,  as  well  as 
the  bearing  of  the  anterior  or  posterior  groups  on  the 
configuration  of  the  compound,  and  one  unites  -j-  A  with 
H-  A  and  —  A  with  —  A,  for  one  then  obtains  the  follow- 
ing figures  : 


Fig.  4- 


These  difficulties  do  not  present  themselves,  it  is  true, 
in  the  case  of  the  compound  Cabc,  but  it  is  necessary  at 
once  to  take  them  into  account  in  considering  the  figures 
which  represent  a  compound  of  the  type  Cabc — Cabc. 


Fig-  5- 


The  three  configurations  of  a  system  of  this  kind  are 


OPTICAL   ISOMERISM  33 

easily  comprehended  if  one  observes  each  half  system  by 
itself. 

In  these  figures  it  seems  that  the  disposition  of  the 
groups  abc  and  cba  may  have  been  inverted  in  passing 
from  the  inferior  tetrahedron  to  the  superior,  in  the  same 
way  that  configuration  3  which  represents  two  tetrahedra, 
inverted,  seems,  on  the  contrary,  to  be  constituted  of  two 
identical  tetrahedra.  In  looking  at  them  in  the  other 
way  one  observes  that  they  represent  the  configuration 
+  A  —  A. 

These  perspective  formulae  can  be  advantageously 
replaced  by  projection  formulae,1  by  projecting  on  the 
plane  of  paper,  groups  which  are  not  in  this  plane. 

In  this  way  we  obtain  the  following  symbols  for  the 
three  stereoisomers  :  Cabc — Cabc. 


c—  C— a  a—C—c  a—C—c 

I  I 

a — C— c  c—  C — a  a—C—c 

I  I  I 

b  b  b 

-f  2A  —  2A  ±  A 

One  will  remark  that  the  isomer  ±  A  possesses  also  a 
a  plane  of  symmetry,  and  this  is  the  fundamental 
characteristic  which  marks  all  inactive  non-racemic  com- 
pounds. 

We  pass  from  -f  2A  to  -  2A  by  rotating  each 
carbon  atom  with  its  connected  group,  so  that  a  certain 
group  passes  successively,  through  the  space  occupied  by 
two  other  groups,  a  and  c  for  example  ;  two  successive 
rotations  do  not  change  the  sign  of  the  asymmetric  carbon 
atom. 

1  Fischer:  Ber.  d.  chem.  Ges.,  24,  2684. 
3 


34  ELEMENTS  OF  STEREOCHEMISTRY 

More  complicated  configurations  can  in  the  same  way 
be  easily  comprehended  by  using  figures  of  this  kind,  so 
that  in  future  these  formulae  will  be  exclusively  employed 
in  treating  these  cases  of  optical  isomerism. 

c.  Principal  examples  of  isomers  with  several  asym- 
metric carbon  atoms. — In  general,  it  may  be  said,  that 
the  number  of  isomers  that  have  been  observed,  is  in 
perfect  accord  with  theory.  In  the  case  of  complex  com- 
pounds, the  number  may  be  less  than  that  which  theory 
indicates,  but  it  has  never  been  found  greater. 

The  classical  example  of  compounds  of  symmetric 
structure  and  with  two  asymmetric  carbon  atoms  is  that 
of  the  tartaric  acids. 

COOH— CH(OH)— CH(OH)— COOH.     . 

The  laevo-,  dextro-,  and  inactive  tartaric  acids  are  com- 
pounds of  single  molecular  weight  ;  the  racemic  form 
of  tartaric  acid  is  double. 

The  /-  and  ^-tartaric  acids  exhibit  in  their  crystalline 
form  a  hemihedrism  which  is  non-superposable.  The 
racemic  and  inactive  tartaric  acids  are  without  action  on 
polarized  light  and  do  not  present  the  above-mentioned 
crystalline  peculiarity.  The  first  is  cleavable  into  two 
active  components,  the  second  is  not.  The  formulae  may 
be  expressed  as  follows  : 


COOH 

COOH 

COOH 

OH-C—  H 

H—  C—  OH 

H—  C—  OH 

H—  C—  OH 

HO—  C—  H 

H-C—  OH 

| 

1 

| 

COOH 

COOH 

COOH 

Dextro  acid. 

v  — 

Laevo  acid. 

Inactive  non- 

TQ  r»£»triir*   ar*irl 

Racemic  acid. 


OPTICAL,   ISOMKRISM  35 

The  two  synthetic  erythrites  obtained  by  Griner1 
represent  a  racemic  form  and  an  active  non-cleavable  form. 

Dimethyl  tartaric  acid, 

COOH—  C(OH)CH3—  C(OH)CH3—  COOH, 
offers  the  same  peculiarities.2  In  this  group  of  com- 
pounds it  is  necessary  again  to  class  the  numerous  sym- 
metrical substitution  products,  and  in  particular  the  dialkyl 
derivatives  of  succinic,  glutaric,  adipic,  and  pimelinic 
acids,  corresponding  to  the  following  structural  formulae, 
COOH  COOH 

CH—  CH  and 

/    \ 

COOH  COOH 

\  / 

CH—  (CH2)MCH 

R  R 

The  borneols3  are  characterized  by  two  asymmetric 
atomic  groupings  differing  from  one  another,  if  one 
adopts  Kekule's  view.  On  the  other  hand  Bredt 
assumes  camphor  to  have  three  of  these  groups  : 


yv  CH2  —  CH 

H2C  CH2 

H2C  CH(OH) 


CH3 

Kekule. 

1  Compt.  rend.,  117,553;  "9.  723- 

2  Fittig:  Ann.  Chem.  (Uebig),  249,  207. 

a  Moutgolfier  and  Haller :  Compt.  rend.,  105,  227;  109,  387;  no,  149. 


36  ELEMENTS   OF   STEREOCHEMISTRY 

From  what  has  been  said  on  page  30,  one  ought  to  find 
at  least  four  active  modifications.  There  have  been 
found  two  laevo-  and  dextrorotatory  modifications  which 
are  stable  and  two  which  are  unstable.  Two  of  these 
isomers  which  are  really  enantiomorphous,  combine 
racemically  to  give  inactive  molecules  of  double  molec- 
ular weight,  and  the  same  properties  are  encountered  in 
the  bornyl  urethanes  investigated  by  Haller.  Other 
examples  may  be  cited  which  are,  however,  less  com- 
plete. Thus  among  the  belladonna  alkaloids1  we 
find  two  atropines  /  and  d  and  the  racemic  modification 
the  ordinary  inactive  alkaloid,  but  besides  these  three 
there  is  yet  hyoscyamin,  laevorotatory,  having  the  same 
structure,  but  which  is  optically  different  from  the  /-atro- 
pine.  The  fourth  isomer  ^-hyoscyamin  has  not  as  yet 
been  isolated. 

The  esters  and  salts  resulting  from  the  combination  of 
an  active  acid  (+  or  — )  with  an  active  base  (-+-  or  — ) 
fall  also  into  the  same  category.  One  may  have  them  as 
compounds. 

i.   -f  acid  -f  alcohol.     2.   -f  acid  —  alcohol. 
3.  --  acid  +  alcohol.     4.   --  acid  —  alcohol. 

The  pentatomic  alcohols,  aralite,2  xylite,3  adonite,4 
having  the  formula 

CH2OH.CHOH.CHOH.CHOH.CH2OH, 
and   the   corresponding   trioxyglutaric     acids,5 

COOH.  (CHOH)3.COOH , 
are  symmetrical  compounds  containing  three  asymmetric 

1  I,adenburg :  Ber.  d.  chem.  Ges.,  21,  3065. 

2  Kiliani :  Ibid.,  20,  1234. 

8  Bertrand  :  Bull.  Soc.  Chim.,  [3],  5,  740. 
*  Fischer  :Ber.  d.  chem.  Ges.,  26,  638. 
6  Fischer  :  Ibid.,  24,  4214. 


OPTICAL   ISOMKRISM  37 

atoms,  and  confirm  the  developments  of  the  theory  found 
on  page  30. 

The  pentoses,  alike  in  structure,  arabinose,  xylose, 
and  ribose,  CH2OH.CH(OH).CH(OH).CH(OH).CHO, 
have  an  unsymmetrical  formula.  These  three  com- 
pounds are  active,  as  are  their  derivatives,  each  having 
a  distinct  rotatory  power,  and  the  existence  of  their 
antipodes  not  being  doubted,  one  conceives  six  isomers 
out  of  eight,  which  theory  demands. 

The  ketoses, 

CH2OH.CHOH.CHOH.CHOH.CO.CH2OH, 
of   which   fructose   is  the  best  known  example,    belong 
also  to  this  group. 

Substances  with  four  asymmetric  carbon  atoms  are 
particularly  interesting,  by  reason  of  their  close  relation- 
ship with  glucose.  Among  the  derivatives  of  this 
class,  the  hexatomic  alcohols,  CH2OH(CHOH)4  CH2OH, 
and  the  tetraoxyadipic  or  saccharic  acids,1 

COOH(CHOH)4COOH, 

are  isomers  of  symmetrical  structure.  L-  and  d- 
mannite,  /-  and  af-sorbite,  df-talite  and  inactive  non-racetnic 
dulcite  are  also  compounds  belonging  to  this  class.2 

Of  the  saccharic  acids  the  following  have  been  isolated  : 
/-  and  ^/-saccharic  acids,  and  /-mannosaccharic  acid,3  d- 
mannosaccharic acid,4  the  inactive  mucic  and  allomucic 
acids,5  /-  and  ^-isosaccharic acids,6  /-  and  d- talomucic  acids.7 

Fischer,  Piloty :  Ber.  d.  chem.  Ges.,  24,  1841,  2684. 

Crossley  :  Ibid.,  25,  2564. 

Kiliani :  Ibid.,  20,  341. 

Fischer :  Ibid. ,24,  539  ;  27,  384. 

Fischer  :  Ibid.,  24,  2137. 

Tiemann  :  Ibid.,  17,  246. 

Fischer  :  Ibid.,  24,  3626. 


38  ELEMENTS   OF   STEREOCHEMISTRY 

In  this  case  we  have  found  by  experiment  the  ten  acids 
indicated  by  theory. 

The  aldoses, 

CH2(OH).CH(OH).CH(OH).CH(OH).CH(OH).CHO, 
are  optical  isomers  of  dissymmetric  structure.  Among 
these  glucose,  mannose,  galose,1  galactose,  and  idose  are 
known  under  both  laevo-  and  dextrorotatory  forms. 
The  detailed  consideration  of  these  compounds  will  be 
made  the  subject  of  another  chapter. 

IV.  FORMATION  OF  ASYMMETRIC  ACTIVE  COMPOUNDS 
a.  Synthesis  of  racemic  compounds  from  symmetric 
substances. — Compounds  with  asymmetric  carbon  atoms 
are  not  always  optically  active,  for  they  present  them- 
selves often  in  the  form  of  equimolecular  mixtures  of 
enantiomorphous  isomers. 

This  is  the  case,  without  exception,  for  all  the  products 
obtained  by  synthetic  methods.  Compounds  in  an  active 
state  are  not  formed  by  laboratory  reactions,  and  in  order 
to  isolate  them,  recourse  must  be  often  had  to  the  help  of 
living  organisms.  It  was  this  fact  which  led  one  formerly 
to  suppose  that  rotatory  power  is  the  action  of  a  vital 
force. 

L,e  Bel  has  shown2  that  the  transformation  of  a  sym- 
metrical compound,  by  substitution,  or  by  addition  to  an 
asymmetric  compound,  must  always  give  rise  to  equi- 
molecular quantities  of  laevo-  and  dextrorotatory  isomers, 
and,  if  a  symmetrical  molecule  £>abc2  becomes  asymmetric 
by  the  replacement  of  one  of  the  groups  c  by  group 
d(e.g.,  transformation  of  propionic  acid,CH3CH2.COOH, 
into  lactic  acid,  CH3.CH(OH).COOH,  the  two  identical 
radicals  (in  the  above  example,  the  two  hydrogen 

1  Fischer,  Piloty  :  Ber.  d.  chem.  Ges.,  24,  526  ;  Fischer  :  Ibid.,  24,  532. 

2  Bull.  Soc.  Chim.  (2),  22,  246. 


OPTICAL   ISOMERISM  39 

atoms)  being  symmetrically  placed  in  the  molecule,  have 
an  equal  chance  of  being  substituted. 

If  but  one  molecule  participates  in  the  reaction, 
substitution  can  be  effected  with  the  same  probability  on 
one  side  of  the  plane  which  passes  between  the  two  groups, 
c,  as  on  the  other ;  but  as  all  chemical  reactions  take 
place  between  considerable  numbers  of  molecules,  and  if 
substitution  takes  place,  m  times  to  the  right  and  m'  times 

to  the  left,  the   relations,  — , ,  tend  towards  unity,  for   m 

Wls 

+  /»'  increase  beyond  all  limits ;  therefore,  equal 
quantities  of  laevo  and  dextro compounds  will  be  formed, 
and  this  mixture  bears  the  general  name  of  racemic. 

It  is  the  same  in  phenomena  implying  addition 
C2H..CH:CH2  +  HI  =  C2H5.CHI.CH3. 

The  atoms  of  iodine  which  produce  asymmetry  will,  in 
all  probability,  fix  themselves  on  both  sides  of  the  plane 
of  symmetry  in  an  equal  degree,  and  hence  equal  quan- 
tities of  the  two  enantiomorphous  compounds  will  be 
formed. 

b.  Cleavage  of  inactive  mixtures  in  inactive  isomers.— 

Chemical  reagents  act  in  the  same  way  on  laevo-  or  dextro- 
rotatory isomers  of  which  the  combination  has  been 
termed  racemic,  and  one  cannot  then  hope  to  destroy  one 
by  a  chemical  reaction.  It  is  for  this  reason  that  the 
methods  of  splitting  are  founded  on  other  principles,  viz. : 

a.  Action  of  living  organisms,  principally  micro- 
organisms. 

0.  Action  of  compounds  already  provided  with  rotatory 
power. 

y.  Spontaneous  cleavage  with  the  formation  of  enantio- 
morphous crystals. 


40  ELEMENTS   OF  STEREOCHEMISTRY 

These  three  methods  discovered  by  Pasteur  have  been 
used  with  success  in  the  cleavage  of  a  great  number  of 
synthetic  inactive  mixtures,  and  are  to-day  well 
established  modes  of  dealing  with  these  compounds.  On 
the  other  hand,  all  efforts  at  cleavage,  based  on  com- 
bination with  compounds  of  symmetrical  structure  up 
to  the  present,  have  given  negative  results. 

a.  Cleavage  of  inactive  mixtures  by  means  of  living 
organisms. —This  purely  physiological  method  is  the 
oldest  of  the  three  above  mentioned  and  was  used  for  so 
long  a  time  that  it  was  thought  that  no  optically  active 
compound  could  be  formed  without  the  intervention  of 
biological  phenomena.  It  is  probable  that  certain  living 
organisms,  asymmetric  themselves,  or  at  least  containing 
active  asymmetric  compounds,  have  the  power  of  attack- 
ing and  destroying  one  of  the  two  isomers  in  an  active 
mixture.  Hence  it  follows  that  the  products  of  fermenta- 
tion when  containing  an  asymmetric  carbon  atom  are 
nearly  always  optically  active.  To  Le  Bel  is  due  a  large 
number  of  cleavages  based  on  this  method.1  Other 
investigators  have  also  made  interesting  researches  in  this 
way.2 

Examples. — Penicillium  glaucum  which  has  given  such 
good  results  destroys  the  dextro  isomers  of  racemic  acid, 
synthetic  secondary  amyl  alcohol,  CH3.CH(OH).C3H7, 
propylene  glycol,  CH3.CH(OH).CH2OH,  gly eerie  acid, 
COOH.CH(OH).CH2OH,  etc.,  and  thus  permits  the 
isolation  of  the  laevorotatory  isomers.  It  produces  the 
inverse  effect  on  the  following  racemic  compounds : 
primary  amylic  alcohol,  CH3.C2H5.CH.CH2OH,  phenyl 
glycollic  acid,  C6H5.CH(OH)COOH,  lactic  acid,  CH3. 

1  Compt.  rend.,  87,  213 ;  89,  312 ;  92,  532;  etc. 

2  I^ewkowitsch :  Ber.  d.  chem.  Ges.,  15,  1505;  16,  1568,  2721. 


OPTICAL   ISOMKRISM  41 

CH(OH).COOH,  etc.,  and  in  these  cases  it  is  the  left 
modification  which  is  destroyed  and  the  right  which  per- 
sists. It  is  not  a  matter  of  indifference  which  micro- 
organism is  employed  as  all  do  not  act  in  the  same 
manner  on  inactive  mixtures.  According  to  the  ferment 
used  one  may  obtain  the  dextro-  or  laevorotatory  isomer. 
Thus  while  penicillium  glaucum  permits  the  isolation  of 
the  dextrogyrous  phenylgly collie  acid,  saccharomyces 
ellipsoidlus  gives  the  laevorotatory  compound  (Lewko- 
witsch).  Laevolactic  acid  has  recently  been  obtained  by 
the  action  of  a  new  ferment  on  cane-sugar.1  The  active 
compounds  found  in  the  vegetable  kingdom,  the  sugars, 
the  starches,  the  terpenes,  alkaloids,  and  albuminoids  are 
very  numerous  and  we  can  thus  assume  that  the  higher 
plants  also  favor  cleavage.  The  animal  body  seems  less 
prone  to  produce  active  compounds,  but  it  does  so  never- 
theless in  certain  cases  in  quite  the  same  manner  as 
plants  in  the  sense  that  it  destroys  certain  active  modifi- 
cations after  ingestion  of  the  corresponding  racemic  com- 
pound.2 

The  observations  of  Chabrie2  on  the  degree  of  toxicity 
of  the  different  modifications  of  tartaric  acid  furnish  a 
new  and  very  interesting  confirmation  of  the  varying 
action  of  optical  isomers  on  the  organism,  and  Fischer 
and  Thierfelder  have  shown  recently3  that  the  phenomena 
of  fermentation  are  in  direct  relation  with  the  structure 
of  the  compounds  investigated. 

This  method  of  cleavage  is  nevertheless  restricted  in 
its  employment,  for  a  great  number  of  chemical  com- 
pounds oppose  the  growth  of  micro-organisms  and  even 
arrest  it.  This  is,  of  course,  the  case  with  antiseptics. 

1  Schardinger,  Wiener  Monatshefte,  n,  545. 

2  Baumann  :  Ber.  d.  chem.  Ges.,  15,  1731. 

3  Ibid.,  27,  2031. 


42  ELEMENTS   OF  STEREOCHEMISTRY 

On  the  other  hand  does  an  asymmetric  substance  lend 
itself  to  the  culture  of  a  micro-organism,  one  may  be 
fairly  certain  to  effect  splitting  into  one  of  its  isomers. 
In  very  rare  instances  one  has  obtained  the  racemic 
compound,  which  is  the  case  with  ordinary  lactic  acid 
produced  in  the  fermentation  of  ordinary  cane-sugar. 
This  can  be  explained  by  assuming  that  the  micro- 
organisms act  as  readily  on  the  laevo  as  on  the  dextro 
isomers.  It  is  possible  also  that  the  lactic  acid  is  produced 
from  the  fructose  group  only  by  hydrogenization  of  the 
ketone  group,  in  this  way  producing  equal  amounts  of 
both  isomers. 

/3.  Splitting  of  inactive  mixtures  by  means  of  active 
compounds. — This  method  is  based  on  the  fact  that 
inactive  acids,  combined  with  active  bases,  produce  salts 
of  which  the  properties,  and  in  particular  the  solubilities, 
are  different.  These  salts  can  be  separated  by  fractional 
crystallization  and  allow  thus  the  formation  of  the 
active  acids.  Active  cinchonin,  for  example,  permits 
the  separation  of  tartaric,  racemic,  synthetic  inactive 
malic,  phenylgly  collie,  and  phenylbromlactic  acids. 

yCH.OH1 

Quinin  has  been  used  with  tropic  acid,  C6H5CH^  , 

\COOH 

strychnin  with  phenyldibrompropionic  acid,  C6H5.CH- 
Br.CHBr.COOH  as  well  as  with  the  numerous  acids 
synthesized  in  the  sugar  group. 

Conversely  dextrotartaric  acid  has  been  used  in  the 
cleavage  of  synthetic  conicin,  of  the  alkyl  piperidins, 
and  of  tetrahydro-/?-naphthylamin. 

In  all  these  operations  it  is  of  advantage  to  start 
crystallization  by  means  of  a  fragment  of  the  dextro  or 
laevo  salt. 

1  I,adenburg  and  Hundt :  Ber.  d.  chem.  Ges.,  22,  2590. 


OPTICAL   ISOMERISM  43 

The  attempts  to  produce  the  cleavage  of  a  racemic 
alcohol  by  esterification  with  an  active  acid,  and  on  the 
other  hand  of  the  combination  of  a  racemic  acid  with  an 
active  alcohol,  have  so  far  yielded  negative  results. 

y.  Spontaneous  separation  of  inactive  mixtures  by 
simple  crystallization  of  the  two  enantiomorphous  isomers. 

— This  method  has  only  been  successful  in  a  small 
number  of  cases,  as  in  that  by  Pasteur  of  ammonium 
sodium  racemate.  The  solution  of  this  salt  deposits 
under  certain  conditions,  enantiomorphous  hemihedral 
crystals  of  the  /-  and  d  tartrates  which  one  separates  by 
means  of  the  lens  and  forceps. 

Inactive  asparagin,  COOH— CH(NH2).CH2— CONH2, 
prepared  from  fumaric  and  maleic  esters  always  gives,  by 
crystallization,  two  enantiomorphous  modifications.1  This 
method  is  of  considerable  theoretical  importance,  for  it 
allows  us  to  pass  directly  from  inactive  substances  to 
those  having  optical  properties  without  the  intervention 
of  micro-organisms,  as  Jungfleisch  has  proved  that 
dioxysuccinic  acid  prepared  by  starting  from  ethylene 
and  passing  by  means  of  the  bromid,  cyanid,  succinic 
acid,  and  dibromsuccinic  acid  is  a  mixture  of  racemic 
acid  and  inactive  tartaric  acid.2 

Curie  has  indicated  recently  the  interesting  observation 
that  a  mixture  formed  in  a  magnetic  field,  and  an  electric 
field  is  asymmetric,  and  could  perhaps  lend  itself  to 
separation,  and  perhaps  to  the  formation  of  active  sub- 
stances by  purely  physico-chemical  methods.  Experi- 
mental verification  of  this  is  still  wanting.3 

1  Kornerand  Menozzi  :  Gaz.  chim.  ital.,  1887,  226. 

2  Bull.  Soc.  Chim.  [2],  19,  194. 

3  Curie  :  Soci£t6  fran^aise  de  physique,  1894,  53. 


44  ELEMENTS   OF   STEREOCHEMISTRY 

V.  TRANSFORMATION  OF  ACTIVE  INTO  INACTIVE 
COMPOUNDS 

a.  Without  change  of  configuration.     Racemization. — 

The  methods  of  separation  by  means  of  simple  crystal- 
lization very  rarely  give  good  results,  for  the  reason  that 
enantiomorphous  molecules  have  a  certain  tendency  to 
unite  one  with  another  in  the  same  way  that  active 
enantiomorphous  crystals  combine  to  give  symmetrical 
forms.1 

It  is  but  natural  that  an  equimolecular  mixture  of  two 
enantiomorphous  substances  will  be  inactive,  but  up  to 
the  present  these  substances  have  not  been  considered 
as  a  simple  mixture,  but  rather  as  a  very  unstable  com- 
pound. These  compounds  have  received  the  generic 
name  racemic  derived  from  the  simplest  of  this  class  of 
substances,  racemic  acid.  That  it  is  really  a  true  chem- 
ical compound  is  shown  by  its  lesser  solubility  than  either 
of  its  components,  and  its  formation  also  gives  rise  to 
considerable  loss  of  heat  (441  calories).  The  active 
acids  have  a  melting-point  of  170°  C.,  while  that  of 
the  racemic  compound  is  204°. 

In  aqueous  solution  racemic  acid  is  in  great  part 
decomposed  into  its  constituents,  and  the  decomposition 
increases  with  increased  dilution.  Its  well-defined 
character  as  a  true  chemical  compound  has  been  proved 
by  thermochemical  measurements,2  cryoscopy,3  variation 
in  specific  gravity  and  electrical4  properties.5  The  same 
peculiarities  have  been  observed  with  salts  and  esters  of 

1  Gratha:  Pogg.  Ann  ,  158,  214. 

2.  Berthelot  :  Bull.  Soc.  Chim.  (3),  4,  246. 

3  Raoult :  Ztschr.  phys.  Chem.,  i,  186. 

4  Marchlewsksy  :  Ber.  d.  chem.  Ges.,  i5,  1556. 

5  Ostwald  :  Ztschr.  phys.  Chem.,  3,  371. 


OPTICAL   ISOMERISM  45 

racemic  acid1  with  the  fenchons,2  and  it  is  the  same  with 
the  inosites  from  a  thermochemical  standpoint.3 

The  formation  and  the  existence  even  in  the  solid 
state*  of  a  racemic  compound  is  dependent  on  certain 
conditions  of  temperature.5  The  racemic  ammonio- 
sodium  tartrate  is  only  formed  by  the  union  of  the  laevo 
and  dextro  modifications  above  28°  ;  below  this  tempera- 
ture the  right  and  left  compounds  crystallize  out 
separately. 

Racemic  compounds  deport  themselves  as  substances 
containing  water  of  crystallization,  or  as  double  salts, 
since  the  stability  of  compounds  of  this  class  is  depend- 
ent on  certain  conditions  of  temperature.6 

If  certain  enantiomorphous  compounds,  such  as  the 
asparagins,  the  hydrochloride  of  glutaminic  acid  and 
certain  lactones  of  the  saccharic  acids7  have  not  been 
obtained  in  a  racemic  state  but  always  as  a  mixture  of 
the  opposite  crystalline  forms  it  is  due  doubtless  to  the 
fact  that  one  does  not  know  the  conditions  regulating  the 
transformation.  The  converse  has  also  been  found  with 
certain  symmetrical  modifications  of  the  alkyl  succinic 
acids  which  are  probably  racemic  in  character,  but  which 
as  yet  have  not  been  separated. 

b.  Formation  of  inactive  compounds  starting  from 
active  compounds  by  the  influence  of  heat  and  with 
change  in  configuration. — All  active  substances  can, 
under  certain  conditions  of  temperature,  lose  their 
rotatory  power,  being  changed  into  an  inactive  mixture 

1  Anschiitz  :  Ber.  d.  chetn.  Ges.,  18,  1397. 

2  Wallach  :  Ann.  Chem.  (lyiebig),  272,  108. 

3  Berthelot :  Bull.  Soc.  Chim.  (3),  4,  246. 

4  Van't  Hoff  and  Deventer :  Ztschr.  phys.  Chem.,  i,  172. 

5  Wyrouboff  :  Ann.  chim.  phys.  (6),  9,  221. 

6  Van't  Hoff  and  Deventer:  Ztschr.  phys.  Chem.,  i,  65  and  227. 

7  Fischer:  Ber.  d.  chem.  Ges.,  25,  1025. 


46 


ELEMENTS   OF   STEREOCHEMISTRY 


of  the  two  enantiomorphous  isomers;  for  example,  in  the 
case  of  a  laevogyrate  substance  with  n  molecules  there 

will  be  -     molecules  transformed    to    the   dextrogyrate 

variety. 

The  dextro  and  laevo  modifications  of  an  active  com- 
pound having  exactly  the  same  stability,  it  is  evident 
that  if  heat  transforms  one  into  the  other,  equilibrium 
will  be  established  when  the  mixture  contains  the  same 
number  of  molecules  of  both  isomers  ;  and  this  has  been 
proved  by  considerations  based  strictly  on  thermodynamic 
laws.1 

For  example,  ^-tartaric  acid  heated  to  165-175°  C.  is 
transformed  into  racemic  acid  and  inactive  tartaric  acid  ; 
active  phenylglycollic  and  aspartic  acids  become  inactive 
at  1 80°  ;  active  amyl  alcohol  loses  its  activity  when 
heated  with  sodium,  and  leucine,  and  tyrosine  when 
heated  with  baryta. 


Fig.  6. 

Structural  formulae,  even  those  with  defined  spatial 
relations,  are  insufficient  to  give  a  plausible  explanation 
of  these  transformations.  The  passage  of  one  configura- 
tion into  another  can  only  be  conceived  if  one  assumes 
that  two  of  the  groups  bound  to  a  carbon  atom  detach 
themselves,  and  change  places  with  each  other.  It  is 

1  Van >t  Hoff :  Arch.  N£erlandaise,  1886. 


OPTICAL   ISOMKRISM 


47 


here  that  the  difficulty  arises  if  one  keeps  in  mind  the 
idea  that  one  usually  has  of  valence.  It  can,  however, 
be  completely  avoided  if,  according  to  Werner,1  one 
takes  away  the  conception  that  valences  are  attractive 
forces  oriented  in  space.  Werner  assumes  that  affinity  is 
an  attractive  force  acting  at  the  surface  of  the  atom  which, 
for  simplicity,  is  supposed  to  be  spherical  in  shape.  The 
four  radicals  occupy  positions  on  this  sphere  correspond- 
ing to  the  summits  of  a  regular  tetrahedron  because  these 
positions  correspond  to  the  positions  of  greatest  stability. 
Nevertheless,  interatomic  molecular  movements  take  place, 
and  can  be  considered  as  periodic  pendulum-like  oscil- 
lations around  four  points  which  are  the  tetrahedral 
summits,  and  the  amplitude  of  these  oscillations  increases 
with  the  temperature. 

In  the  most  simple  case  the  oscillation  of  the  atoms  a,  b,  c, 


Fig.  7- 


Fig-  8.  Fig.  9. 

d,  can  be  considered  as  taking  place  in  two  planes  perpen- 
dicular to  one  another  as  indicated  by  the  arrows  in 
Fig.  7.  If  the  temperature  is  sufficiently  high,  the 
oscillations  are  sufficiently  large  to  allow  of  the  atoms 
occupying  for  an  instant  the  position  abed  in  Fig.  8. 
In  this  state  the  four  atoms  will  be  found  in  a  plane  of 

1  Vierteljahrsschrift  d.  Ziircher  Naturf.  Ges.,  26,  i. 


48  ELEMENTS   OF   STEREOCHEMISTRY 

symmetry  and  may  come  back  with  equal  probability  to 
the  old  position  Fig.  8  or  to  a  new  one  which  is  the 
enantiomorph  and  which  is  shown  in  Fig.  9.  One 
easily  conceives  that  the  two  modifications  can  be  thus 
formed  in  equal  quantities  and  one  obtains  the  racemic 
compound. 

Such  is,  in  a  few  words,  Werner's  theory  of  transforma- 
tion and  one  can  generalize  this  view  in  the  following  way  : 

The  amplitude  of  atomic  oscillations  increases  when 
the  temperature  is  raised,  the  atoms  of  a  simple  asym- 
metric molecule  pass  through  positions  of  symmetry  and 
come  to  two  positions  which  characterize  a  racemic 
compound. 

Mention  has  been  made  of  a  certain  number  of  active 
compounds  giving  inactive  derivatives.  This  change 
should  certainly  be  attributed  to  a  spontaneous  trans- 
formation of  active  compounds  into  their  racemic 
isomers. 

Racemization  appears  to  depend  on  the  mode  of  forma- 
tion and  the  constitution  of  the  compounds  obtained. 

Thus,  inactive  bromosuccinic  acid, 

COOH .  CH2.  CHBrCOOH, 
obtained  from  active  malic  acid, 

COOH.CH2.CH(OH).COOH, 

has  not  as  yet  been  separated  into  its  isomers.  This  is  a 
striking  case  of  spontaneous  racemization,  for  if  one 
regenerates  malic  acid  from  this  compound  the  product  is 
inactive. 

On  the  other  hand  active  monochlorsuccinic  acid  has 
recently  been  made  by  starting  from  active  malic  acid  by 
treating  it,  not  as  was  formerly  done  by  hydrochloric 
acid,  but  with  phosphorus  pentachlorid.1 

1  Walden  :  Ber.  d.  chem.  Ges.,  26,  210. 


OPTICAL   ISOMERISM  49 

VI.    REVIEW    OF    COMPOUNDS   CONTAINING   SEVERAL 
ASYMMETRIC  CARBON  ATOMS 

a.  General  properties  of  these  compounds. — It  has  been 
shown  that  the  optical  isomers  of  a  compound  containing 
one  carbon  atom  have  identical  properties  with  the 
exception  of  the  sign  of  their  rotatory  power.  This  is 
not  necessarily  true  in  the  case  of  substances  containing 
more  than  one  asymmetric  group. 

With  the  tartaric  acids,  d  and  /  (+  2A)  and  (/—  2A), 
the  isomers  are  the  image,  one  of  the  other,  but  it  is 
different  with  the  inactive  compound  (+  A  —  A).  This 
substance  differs  from  the  others,  not  only  in  that  it  does 
not  exhibit  enantiomorphism,  but  also  because  the  dis- 
tances between  the  atomic  groupings  are  not  the  same. 

This  acid  also  differs  from  its  isomers,  not  only  in  its 
optical  and  crystallographic  properties,  but  in  its 
different  chemical  and  physical  behavior,  especially  in  its 
melting-point,  its  solubility,  and  its  electrical  conduc- 
tivity, and  this  may  be  said  to  hold  good  also  for  other 
non-racemic  inactive  compounds. 

There  are  always,  among  the  different  isomers  containing 
more  than  one  carbon  atom,  two  compounds  of  inverse 
rotatory  power  which  can  unite  to  form  a  third  inactive 
substance.  These  isomers  are  designated  by  the  same 
name,  but  are  distinguished  by  the  letters  'd,  /,  and  i. 
The  ^-glucose  (ordinary  dextrorotatory  grape-sugar) 
has  an  isomer  /-glucose,  and  these  combine  to  form 
z-glucose  or  racemic  grape-sugar.  The  other  isomers 
which  differ  in  their  chemical  properties  carry  other 
denominations,  e.g. ,  the  aldoses  with  six  carbon  atoms  are 
called  d-  and  /-glucose,  d-  and  /-mannose,  d-  and  /- 
gulose,  etc. 
4 


50  ELEMENTS   OF   STEREOCHEMISTRY 

Stereochemical  projection  formulae  permit  one  to  see 
that  certain  reactions  are  dependent  on  configuration.  It 
is  thus  that  one  can  explain  why  in  the  case  of  the  two 
dimethyl  dioxyglutaric  acids  with  the  configurations,  i 
and  2  only,  that  one  which  corresponds  to  Formula  2,  can 
give  a  double  lactone. 

COOHv  /CH3 

>(HO)C  —  CH2  —  C(OH)< 
CH/  XCOOH 

CH3                          CH3                         *  CH3 
HO— C— COOH     HO— C— COOH     O C CO 


H— C— H  H— C— H 


H— C— H 


COOH  — C— OH         HO— C— COOH 

I  I  I 

CH5  CH3  CH3 

2.  i.  3. 

The  portion  of  the  groups  COOH  and  OH  in  Formula 
i  gives  rise  to  a  single  lactone  only. 

b.  Synthesis  of  compounds  containing  several  carbon 
atoms. 

a.  By  means  of  inactive  mixtures.—  This  method  of 
synthesis  leads  generally  to  the  formation  of  inactive 
compounds,  but  one  usually  obtains  at  the  same  time 
several  substances  of  like  structure,  and  which  are  easily 
separated.  These  cases  of  isomerism,  which  at  one 
time  were  inexplicable,  are  in  perfect  accord  with  the 
theory  of  molecular  asymmetry. 

If    one  react  on  a  racemic  compound  containing  one 

asymmetric  carbon  atom,  and  hence  of  the  formula,  -f  A 

-  A,  with  a  second  racemic  compound  of  the  formula 


OPTICAL   ISOMKRISM  51 

-f-  B  —  B,  then   four  stereoisomers  can  be  formed,  vis  : 
with  +  A(-+A  +  * 


4.    —  A  —  ti 

and  of  these  compounds,  i  and  4,  and  3  and  4,  can  unite 
to  give  the  racemic  compounds 

f+  A  +  B" 
L  -  A  - 
and 


r-  A  +  BI 

L+  A  -  Bj  ' 


These  two  racemic  modifications  should  be  different 
from  one  another,  and  hence  by  reason  of  their  different 
behavior  should  be  generally  separated. 

As  an  example  of  the  above  may  be  cited,  the  racemic 
borneols  obtained  by  the  reduction  of  camphor. 

CH3 CH CH2  CH2 CH CH2 

CH3— C— CH,      4-  HQ     = 


3 

CH2 C—     -CO 

CHS 

Bredt's  Formula. 
Other  examples  are  :  the  addition  products  of  the 
general  formula  R.CHBr — CHBrCOOH1  derived  from 
unsaturated  acids,  R.CH  :  CHCOOH.  The  succinic  acids 
substituted  by  different  hydrocarbon  radicals,  COOH. 
CHR'.CHR".COOH,2  the  analogous  glutaric  acids  and  the 
glycols  of  asymmetric  structure,  R'CH(OH) — CH- 
(OH)R".S  All  these  products  have  been  obtained  in  two 

1  Wislicenus :  Ber.  d.  chem.  Ges.,  20,  1010. 

2  Bischoff :  Ibid.,  23,  3422. 

3  Zincke :  Ibid.,  17,  708. 


52  ELEMENTS   OF   STEREOCHEMISTRY 

modifications  which  should  be  racemic,  but  which,  with 
the  exception  of  the  borneols,  have  not  as  yet  been 
separated.  The  general  case  is  simplified  when  the 
synthetic  compound  has  two  identical  asymmetric  carbon 
atoms,  Cabc — Cabc,  and  if  to  a  racemic  compound, 
-f  A  —  A,  one  adds  the  same  compound  +  A  —  A. 
Then  starting  from  4~  A  one  obtains  : 

1.  +  A-f  A 

2.  -f  A  — A 

and  from  —  A 

{3.  -A+.A 
I  4-  --A-A 

The  compounds,  i  and  4  can  unite  to  form  a  racemic 
substance,  while  2  and  3  represent  the  same  substance 
which  is  inactive  from  intramolecular  compensation.  One 
obtains  thus,  two  isomers  which  are  easily  separated 
of  which  the  one  is  cleavable,  while  the  other  is  not. 
The  synthesis  of  the  tartaric  acids  presents  an  excellent 
example.  This  acid  obtained  by  starting  from  dibrom- 
succinic  acid  or  glyoxal-cyanhydrin  is  a  mixture  of 
racemic  acid  and  inactive  tartaric  acid. 

The  dialkylsuccinic  and  glutaric  acids,  the  hydro- 
benzoins  viewed  as  symmetrical  diphenyl  glycols, 
C,H5.CH(OH)— CH(OH)C6H5,  with  their  two  modi- 
fications, are  comprised  in  this  group  of  compounds, 
although  their  separation  into  active  substances  has  not 
as  yet  been  effected.  Of  the  two  isomers  which  are 
formed  in  these  reactions,  one  is  inactive  from  intra- 
molecular causes,  the  other  because  of  extramolecular 
compensation,  and  one  can  in  certain  cases  decide  with 
some  certainty,  which  is  the  racemic  compound  and  which 
is  internally  compensated. 


OPTICAL   ISOMERISM  53 

Thus,  the  dialkylsuccinic  acids  may  be  represented  by 
the  following  stereochemical  formulae  : 

R 
H— C— COOH 

(0  I  (0 

H— C— COOH 

R 

R  R 

H— C— COOH  R— C— COOH 

(2)  I  (r)  (3)  I  (/) 

RC— COOH  H— C— COOH 

I  I 

R  R 


Racemic. 

One  of  the  two  isomers  melts  at  a  temperature  some- 
what higher  than  the  other,  and  is  also  less  soluble. 
It  hence  is  probable  that  it  represents  the  para,  while  the 
other  is  assumed  to  be  the  antipode.  One  can  compare 
the  first  to  racemic  acid,  and  it  thus  represents  a  com- 
bination of  2  with  3,  while  the  anti- derivatives  cor- 
responds to  inactive  tartaric  acid,  and  consequently  can 
be  represented  by  Formula  i. 

P.  Syntheses  by  means  of  compounds  already  active. 
— One  may  easily  introduce  a  new  asymmetric  carbon 
atom,  that  is  to  say,  a  new  element  of  asymmetry  into  a 
substance  already  active. 

The  grouping  of  a  rotatory  power  of  +  A  linked  to 
another  asymmetric  group  ±  B  can  give  rise  to  two 
isomers  (+  A  +  B)  and  (+  A  —  B).  There  is,  there- 
fore, the  formation  of  two  optically  active  isomers  with- 
out the  possibility  of  racemization  taking  place.  Sub- 
stances which  are  produced  in  this  way  can  be  separated, 


54  ELEMENTS  OF  STEREOCHEMISTRY 

and  they  differ  not  only  in  their  rotatory  power  but  in 
their  properties. 

Numerous  examples  can  be  cited  :  e.  g. ,  /-  and  d-cam- 
phor  each  give  two  active  borneols  ;  the  nitrosochlorids 
of  d-  and  /-limonene  furnish  also  four  stereoisomeric  nitrol- 
amins1.  By  the  addition  of  hydrocyanic  acid  and 
saponification  (Winkler's  reaction),  the  same  active 
aldose  or  ketose  gives  two  acids  containing  an  atom  of 
carbon  more  and  with  different  optical  and  physical 
properties,  the  grouping  R' — CO — H  becoming 

N 
I 
R'— C— COOH 

OH 

and  consequently  asymmetric. 
Ordinary  /-arabinose, 

CH2(CH).(CH(OH))3.CHO, 
furnishes  a  mixture  of  two  acids,  viz  : 

Mannonic  acid, 

-f      /OH 
CH2OH—  [CH(OH)]3— CH< 

XCOOH 
and  gluconic  acid, 

/OH 
CH2OH—  [CH  (  OH  )]  3— CH< 

XCOOH 

In  these  transformations  the  two  isomers  can  be  formed 
in  unequal  quantities,  for  by  reason  of  the  primitive  asym- 
metry of  the  original  compound,  one  of  the  two  con- 
figurations of  the  new  asymmetric  group  can  be  more 
stable  than  the  other. 

It  is  for  this  reason  that  in  the  above  reaction,  arabinose 

1  Wallach  :  Ann.  Chem.  (I^iebig),  252,  106. 


OPTICAL   ISOMKRISM  55 

gives  an  excess  of  mannonic  acid  and  little  gluconic  acid,1 
and  the  same  takes  place  in  many  other  like  syntheses  in 
the  sugar  series. 

All  these  isomers  differ  not  only  in  their  physical 
properties,  but  in  their  chemical  behavior,  and  in  their 
stability.  Thus,  of  the  two  isomers,  mannonic  and 
gluconic  acid,  the  first  alone  gives  a  lac  tone. 

c.  Molecular  transformations  of  active  compounds  with 
several  asymmetric  carbon  atoms. — Isomers  having 
several  asymmetric  groups  have  not  all  the  same  stability, 
and  this  is  shown  by  the  readiness  with  which  certain 
members  of  a  group  undergo  change. 

It  seems  that  each  asymmetric  atom  tends  to  take  up 
a  position  of  equilibrium,  which  is  characterized  by 
optical  inactivity,  and  which,  according  to  Werner,  can  be 
conceived  without  supposing  that  the  groups  have  altered 
their  position  only  in  this  case  by  reason  of  the  difference 
in  configuration  of  the  different  carbon  atoms,  each  is 
characterized  by  a  certain  velocity  of  racemization  which 
is  peculiar  to  itself.  In  other  words,  given  an  active 
compound  (+  A  —  B)  susceptible  of  molecular  change, 
and  in  this  compound  the  group  -f  B  is  transformed  more 
easily  into  —  B  than  -f  A  into  —  A,  then  the  compounds 
(-(-  A  —  B)  will  be  formed  in  larger  quantity  and  con- 
sequently the  rotatory  power  will  be  modified. 

If  (-f  A)  be  very  stable  and  (-f  B)  unstable,  or  if  for 
example,  in  the  conditions  of  temperature  under  which 
the  experiment  takes  place,  only  one  of  the  two  groupings 
is  susceptible  to  transformation,  the  reaction  can  be  inter- 
rupted at  the  end  of  the  first  phase.  Such  is  the  case 
when  ^-borneol  is  converted  into  /-borneol  under  the 
action  of  heat,  or  when  /-menthol  changes  to  d- menthol 

1  Fischer:  Ber.  d.  chem.  Ges.,  23,  2611. 


56  ELEMENTS   OF   STEREOCHEMISTRY 

with  sulphuric  acid.1  The  same  takes  place  with  /-man- 
nonic  acid  and  /-gluconic  acids  for  when  heated  with 
quinolin  they  are  partly  changed,  one  into  the  other, 
each  giving  a  mixture  containing  the  two  acids.2 

Inactive  compounds,  containing  several  asymmetric 
carbon  atoms,  react  in  an  analogous  manner.  Racemic 
acid,  when  heated  to  165°,  yields  inactive  tartaric  acid  ; 
the  two  inactive  synthetic  dimethyl  succinic  acids  are 
transformed  one  into  the  other,  on  heating  with  hydro- 
chloric acid. 

The  anti-modification  of  diethyl  succinic  acid  under 
the  same  treatment  yields  the  para  compound,  and  this 
latter  heated  alone  gives  the  anti-acid.3  Certain  chemical 
reactions  favor  these  molecular  changes,  which  can  be 
seen  in  the  behavior  of  the  dimethylglutaric  acids  and 
of  the  bromin  and  hydroxyl  derivatives.4 

VII.   DETERMINATION  OF  THE  CONFIGURATION  OF 
OPTICAL  ISOMERS 

In  order  to  determine  the  absolute  configuration  of  a 
given  molecule,  one  must  fix  the  exact  position  of  the 
atoms  therein,  and  in  order  to  resolve  this  problem,  a 
fundamental  basis  is  lacking.  The  denomination  as  laevo 
and  dextro,  and  of  -f~  and  —  of  the  two  configurations 
which  characterize  the  compound  Q,abcd  are  quite 
arbitrary,  and  have  only  a  relative  significance.  One 
can  speak  then,  for  the  time  being,  only  of  the  relative 
determination  of  the  configuration  of  a  compound,  that 
is  to  say,  to  define  the  relationship  which  a  certain  com- 
pound with  several  asymmetric  carbon  atoms  bears  to  its 
isomers. 

1  Beckmann  :  Ann.Chem.  (I^iebig),  250,  322. 

2  Fischer  :  Ber.  d.  chem.  Ges.,  23,  2616. 

3  Bischoff :  Ber.  d.  chem.  Ges.,  21,  2102;  22,  389  ;   Selinsky  :  Ibid.,  24,  3997. 
*  Auwers :  Ibid.,    25,  3224. 


OPTICAL   ISOMERISM  57 

The  rotatory  power  of  a  compound  allows  the  deduction 
of  the  configuration  of  compounds  with  two  asymmetric 
carbon  atoms  of  identical  structure,  such  as  the  tartaric 
acids,  both  the  /-  and  af-acids,  the  asymmetric  group- 
ingSj  —  CH(OH)— COOH,  should  be  of  the  same  sig- 
nification, and  of  opposite  sign  to  the  non-racemic 
inactive  tartaric  acid. 

Among  the  more  complex  compounds,  mention  will 
be  made  only  of  some  particularly  instructive  cases  which 
are  in  direct  relation  with  the  synthesis,  and  the  deter- 
mination of  the  constitution  of  glucose  and  galactose  by 
Emil  Fischer.1 

In  the  case  of  compounds  with  three  asymmetric  carbon 
atoms  the  pentkes  will  be  first  taken  up.  These  sub- 
stances are  symmetrical  in  constitution  and  the  four 
modifications  (vide  page  30)  can  be  expressed  by  the 
following  projection  formulae. 

CH2OH  CH2OH 

H— C— OH    +  ^  HO-C— H 

i.      H— C— OH    *  2.*  H— C— OH 

I 
HO— C— H  f     H— C— OH 

CH2OH  CH2OH 


CH2OH  CH2OH 

|  I 

H— C— OH  -t                        H— C— OH 

3.   HO-C— H  «•>              4.      H— C— OH 

H— C— OH  +                       H— C— OH 

I  I 

CH2OH  CH2OH 

1  Ber.  d.  chem.  Ges.,  23,  2114  ;  27,  3189. 


58  ELEMENTS   OF   STEREOCHEMISTRY 

Modifications  i  and  2  are  active  and  enantiomorphous, 
while  3  and  4,  having  each  a  plane  of  symmetry,  are  in- 
active. Arabite,  produced  in  the  reduction  of  arabinose, 
is  active.  The  arabites,  /  and  d,  correspond  then  to  i  and 
2.  Xylite,  derived  from  xylose,  andadonite,  the  reduction 
product  of  ribose,  are  inactive.  The  latter  correspond 
then  to  formulae  3  and  4.  The  trioxyglutaric  acids  are 
known  under  the  two  active  forms  i  and  2,  and  under 
the  two  inactive  forms  3  and  4. 

The  two  parent  substances  of  the  pentites,  which  will 
be  treated  of  farther  on, — viz.,  arabinose  and  ribose, — 
have  the  asymmetric  structure, 

CH2(OH)  — [CH(OH)]3— CHO, 

the  central  carbon  atom  possessing  this  asymmetry. 
Dextroarabinose  has  thus  one  of  the  configurations  la 
or  i£,  derived  from  the  preceding  table,  and  laevo- 
arabinose  20,  or  2b,  derived  from  formula  2. 

CHO  Dextroarabinose.  CHO 

H-C— OH  H-C— OH 

I  or  | 

la.  HO— C— H  id.      H— C— OH 

I  I 

HO— C— H  HO— C— H 

I  I 

CH2OH  CH2OH 

CHO         Ivaevoarabinose.  CHO 

I  I 

HO— C— H  HO— C— H 

I  or  | 

20.      H— C— OH  zb,  HO— C— H 

•fta*.       I 

Hlfc-C— OH  H— C— OH 

K|  I 

***     CH2OH  CH2OH 


OPTIC AI,   ISOMERISM 


59 


The  saccharic  or  tetraoxyadipic  acids  are  the  most  im- 
portant derivatives  with  four  asymmetric  carbon  atoms 
and  of  like  structure.  The  following  table  represents  the 
ten  possible  stereoisomers.  The  enantiomorphous  iso- 
mers  are  bracketed  together.  The  numbering  is  based 
on  the  same  system  as  that  used  in  the  scheme  on  page  57. 


i. 
COOH 


4- 
COOH 


2. 

COOH 


3- 
COOH 


H.C.OH  HO.C.H 

I          I 

H.C.OH  HO.C.H 

I 


H.C.OH   HO.C.H 


HO.C.H 


H.C.OH 


HO.C.H     H.C.OH    H.C.OH   HO.C.H 

i       I       !       I 


HO.C.H 

i 

H.C.OH 

i 

HO.C.H 

H.C.OH 

i 

COOH 

COOH 

COOH 

COOH 

5- 
COOH 

9- 
COOH 

6. 
COOH 

10. 

COOH 

HO.C.H 


H.C.OH 


H.C.OH  HO. 


H.C.OH   HO.C.H 


HO.C.H 


HO.C.H 
HO.C.H 
COOH 


H.C.OH  HO.C.H 

I          I 

H.C.OH  HO.C.H 

!       I 

COOH     COOH 


H.C.OH 

I 
H.C.OH 

H.C.OH 

I 
COOH 


6o 


ELEMENTS   OF   STEREOCHEMISTRY 


7- 
COOH 

HO.C.H 

HO.C.H 

I 
HO.C.H 

HO.C.H 

I 
COOH 


8. 
COOH 

HO.C.H 
H.C.OH 
H.C.OH 

HO.C.H 
COOH 


In  this  table  formulae  i  and  4,  2  and  3,  5  and  9,  6  and 
10  represent  enantiomorphous  isomers,  while  7  and  8 
denote  compounds  inactive  by  internal  compensation. 

As  saccharic  acid  formed  by  the  oxidation  of  glucose, 
CH2OH— (CH(OH))4— CHO,  is  active  and  laevo- 
rotatory  it  cannot  be  represented  by  either  formula  7  or 
8.  It  is  also  obtained,  on  the  other  hand,  from  gulose,  a 
stereoisomer  of  ^-glucose,  therefore  it  cannot  conform  to 
formulae  i,  2,  3,  or  14,  as  will  be  seen  by  consideration 
of  the  table  on  page  30.  A  single  compound  of  sym- 
metrical formula  (df- saccharic  acid)  considered  as  a 
derivative  of  two  compounds  ^-gulose  and  ^-glucose  can 
only  be  represented  by  the  formulae  5  to  10.  For 
saccharic  acid  one  has  only  the  choice  between  5  and  9 
and  6  and  10,  which  represent  respectively  enantio- 
morphous isomers.  As  one  has  observed  the  dextro  and 
laevo  modifications  of  this  acid  one  selects,  by  the  follow- 
ing considerations,  formulae  6  and  10  to  represent  these 
isomers : 

Glucose  and  mannose  are  aldoses  of  identical  structure 
except  that  they  differ  by  the  carbon  atom  which  is  next 


OPTICAL   ISOMERISM  6 1 

to  the  aldehyde  group  and  which  is  in  the  following 
formula1  marked  by  an  asterisk. 

CH2(OH)-CH(OH)-CH(OH)-CH(OH)-CH(OH)*-CHO. 

The  derivatives  of  these  two  sugars  are  identical  when 
the  group  — CH(OH)*--  becomes  symmetrical.  They 
both  give  for  example  the  same  osazone.  These  remarks 
also  apply  to  the  monobasic  acids  derived  from  these  two 
aldoses,  the  gluconic  and  mannonic  acids 

CH2(OH)— (CH(OH)),— COOH 

and  the  same  also  with  the  dibasic  acids,  ordinary  sac- 
charic acid  and  mannosaccharic  acid, 

COOH— (CCH(OH))4— COOH. 

But,  if  saccharic  acid  had  the  configuration  6,  or  what 
is  the  same  10,  mannosaccharic  acid  should  correspond  to 
7  or  8  and  consequently  be  inactive.  Mannosaccharic 
acid  is,  however,  active  and  hence  it  follows  that  /-  and 
^/-saccharic  acids  cannot  be  represented  by  formulae  6  and 
10  but  only  by  formulae  5  and  9. 

It  is  impossible  to  absolutely  decide  which  of  the  con- 
figurations, 5  or  9,  correspond  to  the  laevo  or  dextro  acid. 
For  convenience  ordinary  ^-saccharic  acid  will  be  desig- 
nated by  5  and  /-saccharic  acid  by  9. 

Configuration  of  glucose,  mannose,  gulose,  and  fructose. 
— Two  different  asymmetric  aldoses  correspond  to  the 
symmetric  ^/-saccharic  acid  ;  they  are  the  two  aldoses 
which  on  oxidation  give  this  acid  ;  viz. , -^-glucose  and  d- 
gulose,  of  which  the  formulae  are  according  to  the 
preceding  view. 

As  has  been  seen,  these  two  compounds  lead  to  the 
same  derivative  when  the  terminal  alcohol  and  aldehyde 
groups  are  oxidized  to  carboxyl.  That  d- glucose  corre- 

1  Fischer :  Ber.  d.  chem.  Ges.,  24,  1836. 


62  ELEMENTS   OF   STEREOCHEMISTRY 

spends  to  a  and  af-gulose  to  b  is  shown  in  the  following 
way: 

In  being  oxidized  to  saccharic  acid  glucose  gives  as  a 
first  product  ^-gluconic  acid, 

CH2(OH)— (CH(OH))4— COOH. 

This  identical  ^-gluconic  acid  is  formed  at  the  same  time 
with  the  stereoisomeric  mannonic  acid  when  the  nitrile 
of  arabinose  is  saponified. 

CH2(OH)— (CH(OH))3— CHO 

CH2(OH)— (CH(OH))3— CHOH— COOH 

From  a  stereochemical  point  of  view  this  reaction  intro- 
duces a  new  asymmetric  carbon  atom  and  at  the  same 
time  forms  two  stereoisomeric  acids.  From  what  has 
been  proved  on  page  58  regarding  the  constitution  of 
arabinose,  ^-gluconic  acid  derived  from  ^-arabinose  can 
only  be  represented  by  one  of  the  following  four  formulae 
according  as  one  replaces  the  CHO  in  the  two  formulae 
on  page  58  by 

COOH  COOH 

I  or 

H.C.(OH)  (HO).C.H 

Thus : 

COOH  COOH 

HC.OH  *         HO.C.H 

I  I 

HC.OH  H.C.OH 

ia,a.  |  ia,/3.  \ 

HO.C.H  HO.C.H 

HO.CH  HO.C.H 

I  I 

CH2OH  CH2OH 


OPTICAL   ISOMERISM 


COOH 
H.C.OH 
H.C.OH 

H.C.OH 

I 
HO.CH 


CH2OH 


COOH 

HO.C.H 

I 
H.C.OH 

H.C.OH 
HO.C.H 
CH0OH 


In  order  to  pass  from  these  formulae  to  that  of  glucose 
it  is  only  necessary  to  replace  the  carboxyl  by  an  alde- 
hyde group,  and  one  then  sees  that  formula  ia,/3  is  the 
only  one  agreeing  with  either  of  the  two  formulae  deduced 
for  saccharic  acid — in  this  case  formula  b. 

Glucose  should  then  be  represented  by  the  formula  : 


CHO 


HOCH 


H— C— OH 


HO— C— H 

HO— C— H 

I 
CH2ON 


and  mannose 


CHO 

H— C— OH 
H— C— OH 
HO— C— H 


HO— C— H 
CH2OH 


From  these  results  it  follows  that  among  the  formulae 
given  on  page  58  i a  and  20,  are  those  which  should  be 
chosen  to  represent  d-  and  /-arabinose  respectively. 

The  configuration  of  the  other  stereoisomeric  aldoses 
such  as  mannose  and  gulose,  and  of  the  ketoses,  can  also 
be  deduced  in  the  same  manner. 


64  ELEMENTS   OF   STEREOCHEMISTRY 

Gulose  may  then  be  represented  by  formula  a ;  the 
formula  for  mannose  differs  from  that  of  glucose  by  a 
spatial  difference  in  the  asymmetric  group  connected  with 
the  aldehyde  group. 

Mention  may  be  made  here  of  ^-fructose  whose  con- 
figuration may  be  represented  by  the  following  : 

H      OH    OH 

I         I 
CH2OH  —  CO  —  C  —  C  —  C  —  CH2OH 

!      i      I 

HO      H       H 

for  both  ^/-fructose  and  ^-glucose  give  the  same  osazone, 
and  the  ketose  on  oxidation  is  transformed  into  inactive 
tartaric  acid. 

OH  OH 

I         I 
COOH  —  C  —  C  —  COOH 

I         I 
H      H 

Configuration  of  the  glucoheptoses. — By  addition  of 
hydrocyanic  acid  and  saponification,  one  obtains  from 
glucose,  two  compounds,  the  a-  and  y^-glucoheptonic  acids. 

Glucose  having  the  formula 

H  H  OH  H 

!      i      I      I 
CH2OH— CHOH— CHOH— CHOH— CHOH— CHO, 

!      I      ! 
OH     OH     H      OH 

these  two  acids  can  only  be  represented  by  the  following  : 

H      H      OH   H      H 

I        I         I         I        I 
I.     CH2OH  —  C  —  C  —  C  —  C  —  C  —  COOH 

I        I         I        I        I 
OH  OH  H     OH  OH 


OPTICAL   ISOMERISM  65 

H      H      OH  H      OH 

I        I         I         I        I 
II.     CH2OH  — C  — C  — C  — C  — C  — COOH 

I        I         I         I        I 
OH  OH  H     OH  H 

By  oxidation,  each  of  these  is  transformed  into  a  dibasic 
acid. 

H  H  OH  H  H 

I    I   I    I    I 

r.  COOH  — c  —  c—c  —  c  — c- COOH 

I  I  I  I  I 

OH  OH  H  OH  OH 
H   H  OH  H  OH 

I  I-  I  I  i 

II'.  COOH— C  —  C  —  C  —  C  — C  — COOH 

I  I  I  I  I 

OH  OH  H   OH  H 

Of  the  two  pentoxypimelinic  acids,  one  only  can  be 
active,  for  V  represents  a  symmetrical  compound;  that  is, 
an  inactive  acid  which  is  uncleavable. 

According  to  experiment,  ar-glucoheptonic  acid  gives 
an  active  pentoxypimelinic  acid,  while  the  y#-acid  gives 
an  inactive  compound.  Of  the  two  formulae  above  given, 
I  must  then  represent  the  tf-acid  and  II  the  /^-compound. 
These  two  acids  give,  on  reduction,  two  glucoheptites,  a 
and  ft,  of  which  the  constitution  was  thus  determined.1 

Configuration  of  the  mucic  and  talomucic  acids.2 — 
Rhamnose,  CH3.  (CHOH)4.CHO,  gives  an  oxidation  /-tri- 
oxyglutaric  acid  identical  with  that  obtained  on  the  oxi- 
dation of  arabinose.  The  configuration  of  arabinose  be- 
ing known,  we  have  for  /-trioxyglutaric  acid  the  formula, 

1  Fischer  :  Ann.  Chem.  (I^iebig),  270,  71. 

2  Fischer  :  Ber.  d.  chem.  Ges.,  27,  384. 

5 


66 


ELEMENTS   OF   STEREOCHEMISTRY 

OH  H      H 


COOH— C  —  C—  C— COOH, 

I    I    I 
H   OH  OH 


and  for  rhamnose, 


OH  H   H 


CHVCHOH— C  —  C  —  C— COH, 

?        I    I 
H   OH  OH 

the  sign  ?  being  placed  under  the  group  CHOH  to  indi- 
cate that  its  configuration  is  not  shown  in  this  relation. 

On  the  other  hand,  rhamnose  adds  hydrocyanic  acid 
according  to  Winkler's  reaction  and  on  saponification 
yields  an  tf-rhamnohexonic  acid  which  is  transformed 
into  /5-rhamnohexonic  acid  on  heating  with  pyridin  and 
water  to  140°-! 50°.  According  to  the  formula  for 
rhamnose,  these  two  acids  can  be  expressed  in  the  fol- 
lowing way  : 

OH  H      H      OH 

till 
—  C  —  C  —  C  —  C  —  COOH 

I        I 
OH    OH  H 


CH3  CHOH 


H 
OH  H 


H  H 


II.  CH3  CHOH  —  C  —  C  —  C  —  C  —  COOH 

?     I   I    I    I 

H  OH  OH  OH 

These  acids,  therefore,  differ  only  in  the  relation  of  the 
CHOH  group  with  the  carboxyl. 

Finally,  if  one  oxidizes  <*-rhamnohexonic  acid,  mucic 


OPTICAL   ISOMERISM  67 

acid  is  obtained,  known  for  a  long  time  as  an  inactive 
compound,  and  the  /3-acid  gives,  in  the  same  way,  /- 
talomucic  acid.  These  relations  may  be  expressed  as 
follows  : 

_,  f    <*-rhamno-  (  yfrrhamno- 

Rhamnose  —  { hexonic  acid  —    jhexonicacid 

!  J  J 

/-trioxyglutaric  acid.          Mucic  acid.  /-talomucic  acid. 

It  will  be  shown  farther  on  that  in  these  reactions  the 
methyl  group  is  eliminated.  Then  the  product  of 
oxidation  of  acid  I  has  the  formula  : 

OH  H      H      OH 

I        I         I         I 
I'.  COOH  — C  — C  — C  — C  — COOH 

I        I         I        I 
H      OH  OH  H 

and  that  derived  from  II, 

OH  H      H      H 

I         I        I         I 
II'  COOH  —  C  —  C  —  C  —  C  —  COOH. 

I        I         I         I 
H      OH    OH  OH 

Formula  I'  is  characterized  by  a  plane  of  symmetry. 
It  represents  then  an  inactive  acid,  and  hence  can  be  none 
other  than  mucic  acid.  On  the  other  hand,  II'  repre- 
sents an  active  compound,  and  thus  corresponds  to  /- 
talomucic  acid.  Hence  a-rhamnohexonic  acid  is  rep- 
resented by  Formula  I,  and  /?-rhamnohexonic  acid  by 
Formula  II. 

In  order  to  prove  that  in  these  reactions  the  group 
CH3  is  eliminated,  mucic  acid  will  be  taken  up  as  an 


68  ELEMENTS   OF   STEREOCHEMISTRY 

example.     Being    inactive    it  can   only  be  represented 
by  a  symmetrical  formula  such  as  : 

H      H      H     H 

I         I        I 
COOH  — C  — C  — C  — C  — COOH, 

I        I        I 
OH  OH  OH  OH 

or  equally  well  by 

OH  H     H      OH 

i        I         I        I 
COOH  — C  —  C  —  C  —  C  — COOH. 

I         I        I        I 
H      OH  OH  H 

One  sees  at  a  glance  that  both  these  formulae  are 
incompatible  with  that  of  rhamnose  when  the  trans- 
formation of  that  compound  into  mucic  acid  would  result 
from  the  replacement  of  the  groups,  CH3  by  COOH  and 
the  elimination  of  CHO.  In  this  way  have  the  formulae 
for  mucic  and  /-talomucic  acids  been  definitely  established. 

Configuration  of  dulcite,  galactose,  talose  and  the  galac- 
tonicand  talonic acids.— Galactose,  CH2OH— (CHOH)4— 
CHO,  gives  on  oxidation  mucic  acid  and  on  reduction 
dulcite,  CH2OH.(CHOH)4.CH2OH,  a  compound  which 
for  some  time  was  believed  to  be  active  but  which  has 
since  been  found  to  be  without  action  on  polarized  light. 

The  configuration  of  mucic  acid  being  established  the 
formula  for  dulcite  will  be 

OH  H      H      OH 

I         I         I         I 
CH2OH— C  —  C  —  C  —  C  — CH2OH 

I         I         I         I 
H      OH  OH  H 

and  for  galactose 


OPTICAL   ISOMERISM  69 

OH  H      H      OH 

A.  CH2OH  —  C  —  C  —  C  —  C  —  CHO 

I         I         I        I 
H      OH    OH  H 

or  equally  well 

H      OH  OH    H 

I         I         I         I 

B.  CH2OH  —  C  —  C  —  C  —  C  —  CHO 

I         I         I         I 
OH  H      H      OH 

according  as  the  group  CHO  is  placed  to  the  right  or  to 
the  left  of  the  chain  of  asymmetric  carbon  atoms. 

On  the  other  hand,  the  first  product  of  the  oxidation  of 
galactose  is  galactonic  acid, 

CH2OH.CHOH.CHOH.CHOH.*CHOH.COOH, 

which  heated  with  pyridin  and  water  to  140°-!  50° 
is  converted  into  talonic  acid.  By  analogy  with 
the  other  compounds  so  far  studied  this  compound 
differs  from  the  others  only  in  the  arrangement 
of  the  group  CHOH  marked  *,  and  which  is  nearest 
the  carboxyl  group.  Further,  this  talonic  acid, 
when  oxidized  by  nitric  acid,  gives  af- talomucic  acid  the 
antipode  of  /-talomucic  acid,  the  constitution  of  which 
has  already  been  established.  This  permits  us  to  assign 
to  these  different  compounds  the  following  configuration 
starting  from  /-talomucic  acid, 

OH  H      H      H 

I         I         I         I      ' 
COOH  —  C— C  —  C  —  C  —  COOH. 

I         I         I         I 
H      OH   OH   OH 

Its  isomer,  d- talomucic  acid,  will  be 


70  ELEMENTS   OF   STEREOCHEMISTRY 

H      OH  OH  OH 

I         I        I         I 
COOH  —  C  —  C  —  C  —  C  —  COOH. 

I         I         I         I 
OH  H      H      H 

From  this  formula  one  may  deduce  two  possible  con- 
figurations for  talonic  acid,  according  as  the  group  CH2OH 
derived  from  COOH  is  placed  to  the  right  or  left  of  the 
carbon  chain. 

H        OH  OH  OH 

I          I          I        I 

C.  CH2OH  —  C  —  *C  —  C  —  C  —  COOH 

I          I         I        I 
OH    H       H     H 

H      OH  OH  OH 

I       I       !       I 

D.  COOH  —  *C  —  C  —  C—  C  —  CH2OH 

I        I        I        I 
OH  H     H     H 

Galactonic  acid  differs  only  in  the  position  of  the  asym- 
metric carbon  atom  C*,  and  can  be  represented  by  either 
of  the  following  two  formulae  : 

H   OH  OH  H 

I    i    I    I 

E.  CH2OH  —  C  —  C-C— C-  COOH 

I       I    I 
OH  H   H  OH 

OH  OH  OH  OH 

I    I   I    I 

F.  CH2OH  — C  —  C  —  C  —  C  —  COOH 

!      I   I 

H   H   H  H 

These  then  lead  to  formulae  for  galactose  which  can 
be  expressed  as  follows  : 


OPTICAL   ISOMKRISM  71 

H   OH  OH  H 

I    I   I    I 
G.     CH2OH  —  C  —  C  —  C  —  C  —  CHO 

I   I    I 
OH  H   H   OH 

OH  OH  OH  OH 

I       I 
H.     CH,OH.  C  — C  — C  — C  — CHO 

I    I    I    I 
H   H   H   H 

The  formulae  G  and  H  on  being  compared  with  A 
and  B  for  which  proof  has  been  given  above,  B  is  seen  to 
be  identical  with  G.  Galactose  is  hence  represented  by 
B  or  by  the  identical  G.  Further,  galactonic  acid  will 
be  K  and  talonic  acid  C.  Lastly,  talose  the  aldose 
derived  from  talonic  acid  can  be  expressed  as  follows  : 

H      OH  OH    OH 

I        I         I        I 
CH2OH— C  —  C  —  C  —  C  —CHO 

I  I        I 

OH  H      H      H 

VIII.  RELATION  BETWEEN  CONSTITUTION  AND   ROTA- 
TORY POWER.     MOLECULAR  ASYMMETRY 

In  an  asymmetric  molecule  Cabcd,  the  nature  of  the 
four  groups  bound  to  carbon  ought  evidently  to  exercise 
a  certain  influence  on  the  magnitude  of  the  rotatory 
power.  Nevertheless,  in  an  homologous  series  of  active 
compounds,  this  constant  can  vary  considerably,  even  to 
changing  its  sign  when  a  compound  very  nearly  allied  is 
examined.  Thus,  the  methyl  ester  of  diacetyl  tartaric 
acid  is  laevorotatory,  while  the  ethyl  ester  turns  the 
plane  of  polarized  light  to  the  right. 

Biot  announced  some  time  since,  that  the  considerable 


72  ELEMENTS   OF   STEREOCHEMISTRY 

differences  observed  in  the  rotatory  power  of  tartaric  acid 
in  dilute  solutions,  was  due  to  the  formation  of  hydrates. 
Later,  Bechamp1  has  demonstrated  that  the  phenomenon 
of  birotation  observed  by  Dubrunfant  in  sugar  solutions 
te  also  due  to  hydration.  In  the  case  of  sugar  one  finds 
that  the  rotatory  power  at  the  end  of  twenty- four  hours 
is  constant  and  is  equal  to  about  half  that  observed  in 
operating  with  fresh  solutions.  This  view  has  been  held 
by  Tollens2  and  by  Jacobi.3  It  is,  however,  not  the  only 
possible  explanation. 

In  1890,  Crum-Brown,4  and  Guye5  indicated  inde- 
pendently the  relation  between  the  rotatory  power  and 
the  groups  bound  to  the  asymmetric  carbon  atom. 

Crum-Brown  assigns  to  each  group  a  function  which, 
among  other  things,  depends  on  temperature  and  the 
nature  of  the  solvent,  and  which  must  be  experimentally 
determined.  The  product  of  the  differences  between 
the  respective  groups  determines  the  rotatory  power. 

Guye  arrives  at  an  analogous  result  by  the  following 
considerations  : 

If  one  designates  by  dlt  d^  d^  d^  d^  d^  the  distances 
from  the  center  of  gravity  of  a  tetrahedral  scheme  with 
six  planes  of  symmetry  corresponding  to  a  regular 
fundamental  tetrahedron,  the  product  of  these  six  distan- 
ces or  the  product  of  the  asymmetry  should  give  the  size 
and  sign  of  the  rotatory  power.  The  sign  depends  on  the 
sign  of  the  product,  which,  in  turn,  depends  on  the  sign  of 
each  factor — positive  or  negative — according  as  the  distan- 
ces, flf1}  d^  are  to  the  right  or  left  of  the  planes  of  symmetry. 

1  Compt.  rend.,  42,  610,  896;  Bull.  Soc.  Chim.  (3),  9,  511. 

2  Tollens  :  Ber.  d.  chem.  Ges.,  26,  1799. 

3  Ann.  Chem.  (I^iebig),  272,  41 ;  vide  I^ule  :  Ber.  d.  chem.  Ges.,  27,  594. 

4  Proc.  Roy.  Soc.  Edin.,June,  1890. 

5  Compt.  rend.   (3),  3,  595  ;    Ann.  chim.  phys.,  6,  25,  145;  Arch.  sc.  phys. 
nat.,  (3),  26,  97,  201,  333  I  Rev.  Scientifique,  49,  265. 


OPTICAL   ISOMERISM  73 

If  one  takes  into  consideration  (  i  )  that  the  different 
radicals  are  at  different  distances  from  the  carbon  atom 
which  they  saturate  (leverage),  (2)  that  the  attraction 
and  repulsion  exercised  by  the  different  groups  on  one 
another  can  displace  them  from  that  position  which  one 
might  call  normal,  then  the  algebraic  expression  of  the 
product  of  asymmetry  assumes  a  somewhat  complex 
type.  It  resolves  itself  into  a  problem  of  four  masses, 
four  levers,  and  the  twelve  angles  which  determine  the 
orientation  in  space  of  the  four  lever  arms.  As  a  matter 
of  fact  at  present  this  formula  cannot  be  controlled  by 
experiment.1 

If,  however,  one  wishes  to  limit  these  verifications  to  a 
qualitative  investigation  one  may,  for  a  first  approxima- 
tion, suppose  that  the  masses  a,b,c,d,  which  saturate  the 
asymmetric  carbon  atom,  are  concentrated  at  the  summits 
of  a  regular  tetrahedron  and  this  gives  the  following 
formula  which  expresses  the  product  of  asymmetry  and 
consequently  the  rotatory  power  : 


(a  —  b}(a—c)(a  —  dnb  —  c}(b  —  d}  (c—d  ) 

(*  +  j  +  r-f  <ty 

One  can  from  this  formula  deduce  the  following  results  : 
(  i  )  If  two  groups  become  identical,  that  is,  if  the  com- 
pound Cabcd  is  transformed  into  a  symmetrical  substance 
Cabc2  the  product  P  is  reduced  to  zero,  and  consequently 
the  rotatory  power  should  disappear,  a  result  which  con- 
forms with  experimental  data. 

(2)  If  one  passes  from  dextrorotatory  compounds  to 
those  that  are  laevorotatory  one  will  observe  that  the  sign 
of  P  depends  only  on  the  numerator  (the  denominator  is 
always  positive)  and  whatever  may  be  the  manner  in 

1  Guye:  Compt.  rend.,  116,  1378. 


74  ELEMENTS   OF  STEREOCHEMISTRY 

which  the  groups  are  formulated,  in  order  to  pass  from 
one  isomer  to  the  other,  the  number  of  factors  in  the 
numerator  which  change  sign  will  always  be  odd  in 
number.  Hence  the  numerator  will  change  sign  in  order 
to  keep  an  absolute  value.  Experimental  evidence  in 
accord  with  this  shows  that  right  and  left  isomers  have 
the  same  rotatory  power  but  have  opposite  signs. 

(3)  Let  a  derivative  be  supposed  in  which  a  >>b  >>  C>d. 
If  substitutions  be  effected  which  change  a  into  a'  but  in 
such  a  way  that  a  >  b  >  C  >  d,  the  sign  of  the  product, 
will  be  unchanged  and  consequently  all  these  derivatives 
will  be  of  the  same  sign  as  the  original  compound. 

Of  the  forty  derivatives  of  ^-amyl  chlorid  known, 
which  are  made  by  replacing  the  group,  CH2C1  by 
groups  heavier  than  C2H5  =29,  all  are  dextrorotatory.1 
(The  number  is  actually  more  than  sixty. ) 

Methyl  glycerate,  CH2OH.CHOH.COOCH3,  prepared 
by  Frankland  and  MacGregor,2  is  laevorotatory,  and  all 
the  other  esters  in  like  manner  prepared  to  the  octylic 
ester  are  also  of  the  same  sign. 

Methyl  tartrate, 

HO  COOCH, 

\/ 
C 

/\ 
H  CHOH.COOCH3 

is  dextrorotatory,  and  the  same  holds  good  for  the 
simple  esters  of  tartaric  acid  according  to  the  researches 
of  Pictet  and  Freundler. 

(4)  Given  a  compound   in  which  a  >  b  >  C  >  d  one 
can  arrange  the  unequal  masses  in  the  following  way  : 

a  >  b,  a  >  e,  a  >  d,  b  >  e,  b  >  d,  c  >  d. 


1  Guye  :  Annales,  6,  25,  145. 

2  J.  Chem.  Soc.,  1893,  511,  1910. 


OPTICAL   ISOMERISM 


75 


If  then  b  be  replaced  by  b'  in  such  a  way  that  the  sign 
of  one  of  the  equations  only  is  reversed  :  e.g. ,  a  <C  b', 
a  >  C,  a  >  d,  b  >  C,  b  >  d,  C  >  d,  one  of  the  factors 
of  the  numerator  will  change  its  sign.  Consequently 
the  rotatory  power  of  the  substituted  compound  will  be 
the  reverse  of  that  of  the  original.  The  same  will  take 
place  if  one  substitutes  for  a  and  b,  a'  and  b'  in  the 
following  way: 

a'  <  b', a'  >  c, a'  >  d,  b'  >  c,  b'  > d,  e> d. 

This  case  is  found  in  the  transformation  of  ethyl  tar- 
trate  into  ethyl  dibutyryl  tartrate,  the  latter  being  laevor- 
otatory.  These  changes  of  sign  which  one  may  foretell 
have  been  observed  in  the  tartaric  ester  series,  and  have 
been  confirmed  by  the  researches  of  Freundler.1 


Diaceyl 

Dipropionyl 

Dtnutyryl 

Divaleryl 

Dibenzoyl 

Methyl 
Ethyl 
Propyl' 
Isopropyl 
Butyl 
Isobutyl 

+  19-87 

-f      2.  II 

+    7-66 
+  12.44 
+  14-89 
+  10.3 

+  ii.  8 
-  15-5 
+    0.3 
+  13.4 
+    5-9 
±    8.0 

+    II-4 
—   I0.7 

+    0.4 
+    5-6 

+    6*9 

+    8.6 

-  I5-I 

-    0.8 

+      5-2 

4-    6.0 

+      7-4 

-  16.1 

—      2.O 

+    3-3 
±    4-8 

42.9 
-    96.6 

68.4 

It  must  be  noted  that  in  each  of  these  derivatives  the 
two  asymmetric  carbon  atoms  are  identical.  The  four 
groups  under  consideration  may  then  be  expressed  as 
follows : 

HO  COOH 

v 

/   \ 
H  CH(OH).COOH 

1  Bull.  Soc.  Chim.  (3),  II,  305-366;  Thesis,  Paris,  1894;  Ann.  chim.  phys. 
1894-1895  ;  Pictet :  Arch.  sc.  phys.  nat.,  Geneva,  1881. 


76  ELEMENTS   OF  STEREOCHEMISTRY 

(5)  If    in   the    preceding    compound  Cabcd,     C    is 
replaced  by  C'.C'  >  a,  one  formulates  the  following: 

a  >  b,  a  <  e',  a  >  d,  b  <  e',  b  >  d,  e'  >  d. 

The  signs  of  the  two  unequal  groups  are  reversed; 
hence  in  the  equation  expressing  the  product  of  asym- 
metry two  factors  will  change  their  sign,  which  is  equiv- 
alent to  saying  that  the  product  P  will  not  change  sign. 

This  case  is  found  in  the  transformation  of  /-malic 
acid, 

HOOC  OH 

V 

/  \ 

H  CH2COOH 

into  propionyl  malic  acid, 

HOOC  OCOC2H5 

/   \ 
H  CH2COOH 

or  in  the  transformation  of  ethyl  malate  into  ethyl 
benzoyl  malate.  These  derivatives  conform  to  the  above, 
in  that  they  are  of  the  same  rotatory  sign  as  their  lower 
homologues.1 

(6)  The  cases  will  now  be  taken  up  of  an  homologous 
series  obtained  from  an  active  alcohol  or  acid  by  replace- 
ment of  the  heaviest  group  a'   in   a  compound  by  the 
groups    «',    a",   a'",    which    are   increasingly   heavier.2 
From  what  has  been  said  under  ( i )  all  these  derivatives 
will  have  the  same  sign.     At  first  sight  it  would  seem 
that  the  rotatory  power  would  constantly  increase.     This 

1  Guye :  Compt.  rend.,  116,  1133;  Colson:  Ibid.,  116,  818. 

2  Guye:  Ibid.,  116,  1451. 


OPTICAL  ISOMERISM  77 

cannot  be  so,  for  if  the  three  factors  (a  — b)(a  —  c)- 
(a  —  d]  increase,  this  increase  will  also  take  place  in  the 
denominator,  but  for  great  values  for  a  the  product  P 

tends  toward  the  limit  ~~6  const.  =  — 3  const.  =  o.      The 

rotatory  power  ought  then  to  reach  a  maximum.  Experi- 
ment confirms  this  view.  This  maximum  has  been 
established  by  Guye  and  Chavanne  in  the  case  of  the 
esters  of  valeric  acid,  in  those  of  gly eerie  acid  (Frank- 
land  and  MacQregor),  of  lactic  acid  (L,e  Bel),  secondary 
amyl  alcohol  (Le  Bel),  the  mixed  oxids  of  primary 
amyl  alcohol  and  the  fatty  esters  of  the  same  (Guye  and 
Chavanne) ,  the  saturated  hydrocarbons  containing  an 
active  amyl  radical  (Welt) ,  the  esters  of  active  ot- 
oxybutyric  acid  (Guye  and  Jordan).  The  most  com- 
plete series  is  the  following,  comprising  the  aliphatic 
esters  of  primary  amyl  alcohol  : 


Amylformate +  2.01 

Amyl  acetate •  •  +  2.53 

Amyl  propionate +2.77 

Amyl  butyrate  n +2.69 

Amyl  valerianate  n 4-  2.52 

Amyl  caproate -f-  2.40 


L^J  D- 

Amyl  heptylate  n 4-  2.21 

Amyl  caprylate  n -\-2.iQ 

Nonylate  n -j-  1.95 

Laurate  n -j-  1.56 

Palmitate  n -j-  i  .45 

Stearate  n -f  M5 


Among  all  physical  chemical  properties  so  far  investi- 
gated, none  have  pointed  to  the  establishment  of  a  max- 
imum ;  boiling-points,  densities;  molecular  refraction, 
specific  heat,  etc. ,  point  to  a  function  which  is  constantly 
increasing,  or  is  asymptotic.  The  rotatory  power  is  the 
first  example  of  a  maximal  point,  and  it  is  interesting  to 
note  that  this  is  foreseen  by  the  formula  above  given. 

If  the  simplified  equation  for  the  product  of  asymmetry 
holds  in  a  certain  number  of  cases,  it  is  insufficient  in 
many  others.  For  example,  if  two  of  the  masses  become 


78  ELEMENTS   OF   STEREOCHEMISTRY 

equal,  the  rotatory  power  should  become  zero.  Numerous 
investigations,  however,  show  that  this  is  not  the  case  ; 
one  is  acquainted,  on  the  other  hand,  with  many  isomeric 
compounds  of  very  like  structure  which  have  not  the 
same  rotatory  power.1  The  researches  of  lyeBel2  have 
shown  that  halogen  derivatives  are  frequent  exceptions 
to  the  rule  given  above,  and  other  exceptions  of  the  same 
kind  have  since  been  indicated  by  Frankland  and 
MacGregor,  Guyeand  Jordan,  and  by  Waiden. 

The  hypothesis  according  to  which  the  masses  are 
concentrated  at  the  summits  of  a  regular  tetrahedron  is 
evidently  too  simple,  and  does  not  correspond  to  fact.  It 
will  be  necessary,  probably,  to  take  into  account  the  arms 
of  the  levers,  and  the  angular  deformations  produced  by  the 
influence  of  the  groups  on  one  another.  Unfortunately, 
experimental  data  do  not  furnish  us  with  the  means  of 
taking  into  account  these  functions. 

Compounds  with  several  asymmetric  carbon  atoms. — 

The  preceding  explanations  have  related  to  s  ubstances 
characterized  by  one  asymmetric  carbon  atom,  or  by 
several  asymmetric  carbon  atoms  which  were  identical,  as  in 
the  case  of  the  tartaric  acids.  The  optical  effects  in  the 
cases  now  under  consideration  correspond  to  the  latter. 
Researches  have  been  undertaken  to  formulate  a  law 
by  which  these  cumulative  effects  are  controlled,  until 
now  only  the  more  simple  cases  have  been  studied,  and 
they  appear  to  be  governed  in  the  following  ways  :3 

1  Goldschimdt  and  Freundt  :  Ztschr.   phys.   Chem.,  14,  3;  Waiden:  Ibid., 
15.  638. 

2  Bull.  Soc.  Chim.  (3),  9,  674. 

s  Guye  and  Gautier :  Compt.  rend.,  n9,  740  and  954  (1894);  Bull.  Soc. 
Chim.,  (3),  9,  403  ;  ii,  1170  ;  13,  475. 


OPTICAL,   ISOMKRISM  79 

I.  Principle  of  the  Independence  of  the  Optical  Effects  of  Asym- 
metric Carbon  Atoms 

In  a  molecule  containing  several  asymmetric  carbon 
atoms,  each  acts  as  if  the  rest  of  the  molecule  were 
inactive. 

II.  Principle  of  Algebraic  Accumulation 

The  effect  of  the  different  asymmetric  carbon  atoms 
in  a  molecule,  add  themselves  algebraically.  From  these 
two  principles  one  can  deduce  the  following  consequences  : 

The  rotatory  power  of  a  compound  can  be  estimated  by 
evaluating  the  optical  effect  of  each  asymmetric  carbon 
atom,  and  taking  the  algebraic,  sum  of  these  different  num- 
bers for  a  result. 

Example. — The  rotatory  power  of  amyl  ether  (amyl 
oxid)  with  two  asymmetric  carbon  atoms, 

CH3v  /C2H5 

>CH  —  CH2  —  O  —  CH2—  CH< 

C,H/  \CH3 

should,  according  to  this,  be  equal  to  double  the  rotatory 
power  of  amyl  oxid  obtained  by  reacting  on  inactive 
isoamylate  of  sodium  with  active  amyl  bromid.  The 
experimental  results  are  the  following  : 

MD. 
Oxid  with  two  active  radicals  L/  =  0.5 ....   +0.49 

Oxid  with  amyl  and  isoamyl  groups +  o.  29 

Oxid  with  one  active  radical -f~  0.25 

For  the  same  reasons  diamyl  will  give  a  value  [#]  D 
equal  to  about  double  that  observed  with  isobutyl-amyl.1 

Wo 

Propyl  amyl +6.23 

Isobutyl  amyl +  5.88 

Diamyl +  12.08-11.95 

i  Welt :  Compt.  rend.,  1895 ;  Bull.   Soc.  Chim.  (3),  11,  1184. 


80  ELEMENTS   OF   STEREOCHEMISTRY 

Amyl  valerate  derived  from  </- valeric  acid  and  /-amyl 
alcohol  will  have  a  rotatory  power  nearly  equal  to  that  of 
amyl  valerate  made  by  starting  from  active  valeric  acid, 
and  inactive  amyl  alcohol  increased  by  the  rotatory  power 
of  amyl  valerate,  formed  by  starting  from  an  active 
alcohol  and  an  inactive  acid : 

MD. 

Valerate  (active)  of  amyl  (inactive) -|-  4.26 

Valerate  (inactive)  of  amyl  (active) +  1.08 

Sum +5-34 

Valerate  (active)  of  amyl  (active) -\-  5.32 

Analogous  verifications,  all  confirming  the  above  prin- 
ciple, have  been  made  with  amyl  glycolate  of  amyl  (Guye 
and  Gautier),  oxybutyrate  of  amyl  and  valeryl  oxy- 
butyrate  of  amyl  (Guye  and  Jordan),  and  with  many 
lactic,  malic,  and  tartaric  esters  (Walden). 

Polar imetric  observations. — The  above  are  shortly  the 
relations  already  found  to  exist  between  the  rotatory 
power  and  stereochemical  structure. 

It  is  important  to  add  that  the  conditions  under  which 
these  relations  are  observed  should  be  of  definite  order  and 
it  is  on  this  account  that  many  cannot  be  used  for  the 
study  of  molecular  asymmetry.  For  the  most  part 
observations  on  substances  dissolved  in  water  should  be 
excluded,  especially  those  on  metallic  salts  of  active 
acids,  or  on  salts  formed  by  active  bases  and  mineral 
acids,  for  one  can  only  estimate  the  resultant  of  the 
derivations,  due  on  the  one  hand  to  the  decomposed  salt, 
and  on  the  other  to  that  which  remains  undecomposed, 
and  this  decomposition  can  equally  well  take  place  as 
splitting  into  acid  and  base  or  into  ions.1 

i  Ostwald:  I,ehr.  d.  allg.  Chem.,  2d  Ed.,  i,  497;  Van't  Hoff:  laager,  der 
Atome  im  Raume,  1894,  p.  100. 


OPTICAL   ISOMERISM  8 1 

Hydrates  may  also  be  produced,  for  it  is  well  known 
that  the  salts  of  tartaric  acid,  for  example,  are  deposited 
from  their  solutions  as  crystals  containing  water  of 
crystallization.  It  may  be  added  also  that  the  relations 
of  the  influence  of  the  solvent  to  the  rotatory  power 
have  been  formulated  through  a  careful  study  of  most  of 
the  observations  taken  by  Guye  and  Rossi.1 

It  was  believed  that  observations,  effected  in  solutions 
of  organic  solvents,  were  outside  this  cause  of  error,  and 
Landolt  has  strongly  supported  this  view,  but  Freundler 
has  shown  that  solvents,  apparently  without  influence  on 
the  dissolved  compound,  can  alter  profoundly  the  rotatory 
power  of  a  substance  and  that  this  alteration  is  accom- 
panied by  cryoscopic  anomalies.  Hence  Freundler 
affirms  that  polarimetric  observations  of  this  kind  should 
be  controlled  by  the  determination  of  the  freezing-  and 
boiling-points  by  Raoult's  and  Beckmann's  methods,  and 
more  recent  researches  tend  to  support  his  views. 

Wyrouboff  has  in  several  instances  been  able  to 
separate  molecular  compounds  of  the  alkaloids  with  the 
alcohols,  with  chloroform,  and  with  benzene,  and  it  has 
also  been  shown  that  certain  active  acids  do  not  combine 
with  organic  bases  in  solution  in  organic  solvents. 

Cryoscopic  or  ebullioscopic  determinations,  although 
indispensable,  do  not  always  indicate  the  presence  of  these 
molecular  combinations,  but  they  are  of  extreme  value 
in  cases  where  polymerization  or  dissociation  takes  place. 

In  order  to  avoid  these  sources  of  error,  it  is  preferable, 
when  possible,  to  make  observations  on  the  substances 
in  a  fluid  state,  and,  if  this  be  not  possible,  to  employ  the 
same  solvent  for  the  complete  series  of  observations,  for 
Freundler  has  shown  that  the  same  solvent  exerts  nearly 

1  Bull.  Soc.  Chim.  (3),  13,  464. 
6 


82  ELEMENTS   OF   STEREOCHEMISTRY 

the  same  influence  on  all  the  homologues  of  a  series, 
and  observations  thus  made  will  be  very  nearly  com- 
parable. It  is  also  advisable  according  to  Haller  to  use 
solutions  containing  always  the  same  number  of  gram- 
molecules  per  liter. 

Observations  on  the  pure  substance,  even,  are  not 
exempt  from  sources  of  error,  for  according  to  Ramsay 
and  Shields,1  certain  substances  in  the  liquid  state 
are  more  or  less  polymerized.  It  is  hence  evident  that 
all  observations  on  fluids  of  this  class  must  be  made  with 
regard  to  this  property,  and  before  utilizing  them  for  the 
study  of  molecular  asymmetry,  it  will  be  necessary  to 
decide  to  what  extent  this  partial  polymerization  can 
modify  the  rotatory  power.  It  is  doubtless  also  that 
the  conditions  of  temperature  and  the  length  of  the 
column  of  liquid  will  one  day  be  the  object  of  reserve 
conditions.  For  these  reasons  the  study  of  the  relations 
between  the  rotatory  power  and  molecular  asymmetry  can 
advance  but  slowly.  They  also  explain  why  the 
expression  ' '  product  of  asymmetry' '  has  been  the  sub- 
ject of  numerous  criticisms,  notably  by  Colson,  who  sees 
in  the  many  conditions  to  be  observed,  difficulties  which 
appear  practically  unsurmountable.2 


STEREOCHEMISTRY  OF  THE  ASYMMETRIC 
COMPOUNDS  OF  NITROGEN 

The  stereochemistry  of  the  nitrogen  compounds  is  but 
begun,  as  the  experimental  facts  on  which  it  is  based  are 
of  but  very  recent  date. 

It  will  be  shown  farther  on  what  the  relations  are  that 
can  be  established  between  the  compounds  of  carbon  and 

1  Ztschr.  phys.  Chem.,  12,  433. 

*  Compt.  rend.,  115,  729;  116,  322,  818. 


OPTICAL   ISOMERISM  83 

those  of  nitrogen  where  in  an  asymmetric  carbon  group 
Cabed  the  group  (Cd)'"  is  replaced  by  N'".  One  should 
then  obtain  combinations  of  the  formula  (N'"abc)  ;  that 
is,  ammonias  of  asymmetric  structure  and  capable  of 
existing  in  two  enantiomorphous  forms. 

In  order  that  this  may  be  so  it  will  be  necessary  to 
assume  that  the  nitrogen  atom  occupies  the  summit  of  a 
tetrahedron,  and  that  the  other  three  groups  are  distrib- 
uted at  the  other  three  apices.  Up  to  the  present  all 
attempts  made  to  separate  enantiomorphous  isomers  of 

the  formula  N—  b  derived  from  NH3.NH2OH.H2N—  NH2, 


have  been  unsuccessful1  and  it  can  be  regarded  as 
probable  that  in  this  class  of  compounds  the  atom  of 
nitrogen  and  the  three  other  groups  are  situated  in  the 
same  plane,  a  view  which  corresponds  to  that  of  Werner 
on  valence  and  affinity  (vide  p.  46). 

It  is,  however,  quite  the  opposite  when  one  comes  "to 
deal  with  ammonium  compounds  containing  a  penta- 
valent  nitrogen  atom.  Here  one  may  well  assume  the 
existence  of  optical  isomers  for  the  nitrogen  atom  is 
bound  to  four  different  groups,  but  up  to  the  present, 
substances  of  this  kind  have  only  given  inactive  non- 
racemic  compounds.2  The  conclusion  reached  by  L,e  Bel 
is  that  the  rotatory  power  is  absent  in-  all  compounds  in 
which  the  atom  which  gives  the  asymmetry  becomes 
linked  to  two  identical  groups,  and  experiment  has 
shown  that  in  the  case  of  nitrogen  the  only  derivatives 
of  nitrogen  which  can  be  obtained  in  an  active  state  are 

1  Hantzsch  and  Kraft  :  Ber.  d.  chem.  Ges.,  23,  2780  ;  Behrend  :  Ann.  Chem. 

257,  203. 

2  I^e  Bel  :  Compt.  rend.,  112,   724. 


84  ELEMENTS   OF   STEREOCHEMISTRY 

compounds  of  the  following  general  formula  X — N — 
abed.  In  these  compounds  one  may  compare  the  group 
(X  —  N)""  to  the  asymmetric  carbon  atom  (C)""  and 
conceive  therefore  an  asymmetric  nitrogen  atom.  It  is 
then  possible  to  have  two  enantiomorphous  isomers  of 
equal  rotatory  power,  but  with  inverse  signs  and  to  obtain 
synthetically  racemic  compounds  by  synthetic  methods. 
As  an  example  of  the  foregoing,  Le  Bel  has,  by  the 
growth  of  bacteria  in  a  solution  of  methyl  ethyl  propyl 
isobutyl  ammonium  chlorid, 

Cl  —  N(CH3)  (C2H5)  (C3H7)  (C4H9), 

been  able  to  isolate  a  laevorotatory  compound  from  which 
he  has  been  able  to  prepare  derivatives  equally  active. 
Unfortunately  these  substances  are  so  unstable  that  the 
contact  of  acids  diminishes  the  rotatory  power  or  even 
causes  it  to  disappear,  the  active  compound  being  trans- 
formed into  the  racemic  derivative.1  Certain  cases  of 
dimorphism,  probably  related  to  stereoisomerism  have 
also  been  observed  by  L,e  Bel  with  trimethyl  isobutyl 
ammonium  chlorid, 

Cl— N-(CH3)3.(C4H9), 

and  by  Schryver  and  Collie  with  methyl  diethyl  amyl 
ammonium  chlorid, 

Cl-N-(CH3)(C2H5)2(C5Hn).2 

The  platinum  salts  of  these  twro  compounds  present 
themselves  in  two  different  modifications  which  are 
mutually  transformable.3 

Mention  may  also  be  made  of  the  isoconicin  of  Laden- 
burg,  in  which  optical  isomerism  may  be  attributed  to  an 
asymmetric  carbon  atom.  The  two  modifications  are  also 

1  lye  Bel  :  Compt.  rend.,  112,  724. 

2  Chem.  News,  63,  147. 

3  I^eBel:  Compt.  rend.,  no,  141. 


OPTICAL   ISOMERISM  85 

distinguished  by  the  different  solubility  of  the  double 
platinum  salts  in  ether  and  in  alcohol.  As  these  two 
compounds  have  undoubtedly  the  same  structure,  L,aden- 
burg  considers  them  as  stereoisomers  and  assigns  to 
them  the  following  configurations : 


H     H     H     H               C,1 

!      i      1      1             1 

rC  —  C-C  —  C—  N  —  C- 

1        1        I        1         1        I 
H     H     H     H       H      H 

i, 

«—^  and 

H 

i~H 

H 
—  C  — 
H 

H 
C  — 
H 

H 
C  — 
H 

H      C3H7 

N-C-, 
H| 

1  I^adenburg  :  Ber.  d.   chem.  Ges.,  26,  854;  lyadenburg  and  Simon:  Bull. 
Soc.  China.  (3),  9,  801,  949. 


PART  II,— GEOMETRICAL  ISOMERISM 


STEREOCHEMISTRY  OF  UNSATURATED  AND  CYCLIC 
COMPOUNDS,  AND  THE  COMPOUNDS  OF 
•      NITROGEN 


GENERAL  THEORY  OF  SATURATED  AND  UNS4JURATED 
COMPOUNDS 

After  having  explained  shortly  what  is  understood  by 
the  configuration  of  saturated  compounds,  containing  one 
atom  of  carbon,  we  must  return  with  more  detail  to  this 
question,  more  particularly  to  those  compounds  containing 
more  than  one  carbon  atom.  The  difference  which  exists 
between  saturated  compounds  and  those  which  contain  a 
double  or  a  triple  bond  should  be  quite  distinct. 

According  to  the  tetrahedral  theory,  the  molecule  of 
ethane,  the  most  simple  of  the  compounds  containing 
two  carbon  atoms,  will  be  represented  by  two  tetrahedra 
having  a  common  apex,  while  the  other  apices  will  be 
linked  to  six  hydrogen  atoms.  If  one  assume  this 
system  to  be  rigid,  the  six  atoms  of  hydrogen  can  be 
compared  to  those  in  the  benzene  nucleus,  which  are 
bound  to  the  solid  angles  of  a  triangular  prism.  Hence, 
the  disubstitution  products  of  ethane  should  exist  in 
three  isomeric  forms,  analogous  to  those  of  benzene 
(Fig.  12)  ;  that  is,  configuration  corresponds  to  the  struc- 
ture CH2 — CH3,  and  2  and  3  represent  the  two  isomers, 
CH2X — CH2X,  analogous  to  the  ortho  and  para  deriv- 
atives of  the  benzene  series. 


GEOMETRICAL   ISOMERISM 
X       Xi^r ^*iH      X 


H      H 


But  as  isomers  of  this  class  have  never  been  found,  this 
first  assumptionjmust  be  modified  in  order  to  render  com- 
pounds 2  and  3  identical. 


One  arrives  at  this  end  by  assuming  that  the  hydrogen 
atoms  do  not  occupy  an  absolutely  fixed  position  in 
space,  or  in  terms  of  the  valence  hypothesis,  that  the  two 
carbon  atoms  are  mobile  about  the  axis  which  unites 


88  ELEMENTS   OF   STEREOCHEMISTRY 

them.  Hence,  configurations  2  and  3  represent  merely 
two  different  phases  in  interatomic  motion.  The  two 
partial  systems,  CH2X,  being  movable  around  the  con- 
necting bond,  configurations  2  and  3  are  not  clearly 
defined  isomers.  This  statement  does  not  imply  that  a 
like  rotation  is  produced  in  every  case,  for  chemistry, 
on  the  whole,  tends  to  prove  that  the  atoms  in 
the  molecule  exercise  mutual  attractive  force  on  one 
another  towards  the  center  of  the  molecule,  and  hence 
by  analogy  those  which  are  not  directly  bound,  one  to 
another,  should  also  exert  a  like  influence;  besides  these 
groups  whicii  have  the  greater  attraction  for  one  another 
should  be  drawn  nearer  together,  hence,  in  the  ethylene 
chlorid,  configuration  2  should  be  the  more  favorable, 
for  it  is  known  that  the  atoms  of  chlorin  and  hydrogen 
have  a  reciprocal  affinity,  one  for  the  other. 

H  H 

Cl— C— H  Cl— C— H 

i.  |  and  2.  | 

Cl— C— H  H— C— Cl 

I  I 

H  H 

It  must,  however,  always  be  assumed  that  modification 
2  can  be  transformed  into  i  under  the  influence  of  heat, 
which  exerts  a  repelling  force,  acting  contrariwise  to 
affinity.  Experiment  has  not  afforded  proof  of  the 
actual  existence  of  stereoisomers  in  compounds  of  this 
class.  It  is,  hence,  necessary  to  admit  that  the  groups 
CH2X  are  movable  around  one  another  (principle  of 
mobile  union),  or  only  one  stable  position  amog 
all  those  which  can  be  conceived,  and  that  is 
by  reason  of  the  mutual  attraction  of  the  atoms  forming 


GEOMETRICAL   ISOMERISM  89 

the    groups   which    make  up  the  molecule  (principle  of 
favorable  configuration). 


Fig.  12. 

This  does  not  hold  good  in  case  of  unsaturated  com- 
pounds ;  that  is  to  say,  in  compounds  containing  two 
atoms  of  carbon  united  by  a  double  bond  such  as  the 
derivatives  of  ethylene, 


These  derivatives  should  be  represented  by  a  scheme 
in  which  two  tetrahedra  are  united  by  two  summits  each 
or  by  an  edge. 

Such  configuration  does  not  allow  of  the  supposition 
of  free  rotation,  for  oscillation  in  such  a  case  is  incon- 
ceivable, hence  the  four  atoms  or  radicals  united  to  the 
carbon  atoms  should  occupy  a  fixed  position  to  one 
another. 

The  groups  ab  of  a  compound  abQ,=Ccd  cannot  then, 
in  accordance  with  the  principle  of  favorable  configura- 
tion, change  places  or  shift  to  position  Cc  or  d,  and  thus 
compounds  of  the  general  formula  abC=Cab  will  give 


90 


ELEMENTS   OF   STEREOCHEMISTRY 


isomers   corresponding  to  the  configurations  of  Fig.  13. 

Jk 


a— C— b 

II 

(c)a     C-b 
I. 


and 


a— C— b 

(d}b     C— «( 
II. 


Isomers  corresponding  to  formula  I  in  which  identical 
groups  are  placed  in  close  relation  with  one  another, 
have  a  plane  of  symmetry  perpendicular  to  the  axis  of 
the  double  bond,  and  are  called  plane  symmetric  or  "cis  " 
isomers. 

Those  corresponding  to  configuration  II  have  a  center, 
but  no  plane  of  symmetry,  and  are  called  axial  central 
trans  or  "  cistrans"  modifications.1 

When  lastly  the  carbon  atoms  are  united  by  a  triple 
bond,  as  in  #CEEC£  as  is  the  case  of  acetylene  and 
its  derivatives,  the  configuration  may  be  represented  by 
Fig.  14. 

1  The  terms  "  plane  symmetric  "  and  "  axial  symmetric  "  are  only  exact  for 
compounds  of  the  formula  abC=Cba.  They  cease  to  be  so,  however,  when 
the  four  H  of  ethylene  are  replaced  by  four  different  groups — where  plainly 
compounds  represented  by  abC=Ccd  have  no  center  of  symmetry.  Hence  it 
is  in  all  cases  preferable  to  designate  geometrical  isomers  by  cis  and  trans. 


GEOMETRICAL   ISOMERISM 


This  mode  of  union  plainly  does  not  admit  of  isomerism. 

Experimental  evidence   is   quite   in   accord   with  the 

foregoing     theory    regarding     isomerism.     Geometrical 


isomerism  is  found  only  in  the  derivatives  of  ethylene  in 
which  group  of  compounds,  numbers  of  isomeric  deriva- 
tives have  been  investigated. 

I.  STEREOCHEMISTRY    OF    THE    UNSATURATED    COM- 
POUNDS OF  CARBON.     ISOMERISM  IN  THE 
ETHYLENE  GROUP 
a.  General  Properties 

As  will  be  seen,  stereochemical  isomerism  in  the  group 
of  ethylene  compounds  is  very  different  from  that  ob- 
served in  the  derivatives  with  asymmetric  carbon,  pre- 
viously studied.  Compounds  of  the  general  formula 
abC=Cab  are  symmetrical  in  structure,  and  are  hence 
inactive,  and  all  attempts  to  split  them  into  optical 
derivatives  have  led  to  negative  results. 

According  to  the  theory  of  molecular  asymmetry  it  is 
not  impossible  that  the  compound  abC=Ced  might  exert 
optical  activity,  and  this  view  was  at  first  believed  to  be 
confirmed  by  the  finding  of  active  modifications  of  citra- 
conic  and  mesa  conic  acids, 

COOHCH=CCH3COOH, 


92  ELEMENTS   OF   STEREOCHEMISTRY 

produced  by  the  action  of  ferments  on  these  acids,  but 
the  researches  of  Le  Bel  showed  that  the  active  com- 
pounds so  obtained  were  products  of  reduction  and  hence 
derivatives  of  malic  acid  which  is  characterized  by  an 
asymmetric  carbon  atom.1 

One  clearly  denned  difference  between  optical  isomers 

•   and  geometrical  isomers  is,  that  with  the  first,  the  distance 

between  the  groups  bound  to  the  carbon  atom  is  equal; 

with  the  second  there  is  a  difference  which  will  be  seen 

by  glancing  at  the  following  formulae  : 

a  —  c—b  a  —  c  —  b 

\\  and  i| 

a  —  c  —  b  b  —  c —  a 

Geometrical  ethylene  isomers  differ  then  fundamentally 
in  their  physical  properties  crystalline  form  (absence  of 
enantiomorphism),  solubility,  density,  and  in  their  melt- 
ing- and  boiling-points  and  they  have  also  different 
chemical  properties  due  to  the  reciprocal  action  of  the 
different  groups  on  one  another.  The  difference  in  their 
electrical  conductivity  which  serves  as  an  indication  of 
their  intramolecular  affinity,  and  certain  other  intra- 
molecular reactions  which  will  be  spoken  of  further  on 
show,  here  also,  that  in  this  class  of  compounds,  isomers 
have  not  the  same  stability,  and  this  is  also  confirmed  by 
the  results  furnished  by  investigation  of  the  amount  of 
heat  evolved  on  combustion. 

Principal  groups  of  geometrical  isomers. — Among  the 
X  group  of  ethylene  hydrocarbons,  stereoisomerism  is  not 
as  yet  known  with  certainty.  It  seems  first  to  make  its 
appearance  in  the  halogen  and  nitro  derivatives,  e.g. ; 

CH3.CH:CHC1 
CH3.CBr  :  CHCHS 
CH3.CBr:CBrCH3 

1  Bull.  Soc.  Chim.  (3),  ii,  292. 


GEOMETRICAL   ISOMERISM  93 

and  particularly  in  the  two  dichlorids  and  dibromids  of 
tolene,  C6H5CX  :  CXC6H5,  distinguished  by  their  crystal- 
lographic  features,  and  also  in  the  two  orthodinitro- 
stilbenes,  C6H4.NO2.CH  :  CH.C6H4.N<V 

Griner2  has  indicated  that  hydrocarbons  possessing 
two  double  bonds,  present  geometrical  isomerism.  Thus, 

CH3— CHI— CH2— CH  =*  CH2 

treated  with  alcoholic  potash  gives  a  mixture  of  two 
hydrocarbons  corresponding  to  the  formula, 

CH3— CH= CH— CH2— CH— CH2, 

which  are  two  geometrical  isomers  giving  two  distinct  tet- 
rabromids.  Examples  of  this  are  more  numerous  with 
the  monocarboxylic  acids.  Thus  are  known:  crotonic  and 
isocrotonic  acids,  CH3.CH:CH.COOH;  angelic  and  tiglic 
acids,  CH3.CH:CCH3COOH  ;  oleic  and  elaidinic  acids, 
C15H31.CH:CHCOOH;  erucic  and  brassidic  acids,  C19H39.- 
CH:CH:COOH;  the  following  halogen  acids:  the  two 
halogen  acrylic  acids,  CHX  :  CHCOOH  ;  two  <*-chloro- 
crotonic  acids,  CH3CH  :  CC1.COOH  ;  two  /?-chloro- 
crotonic  acids,  CHsCBr :  CHCOOH.  In  the  aromatic 
series  may  be  mentioned,  cinnamicand  isocinnamic  acids, 
C6H5.CH:  CHCOOH;  and  the  a-  and  /^-bromine  acids 
derived  from  them,  and  certain  cyclic  acids  as  the  cumaric 
acids,  C6H4OHCH  :  CHCOOH. 

The  unsaturated  dibasic  acids  are  represented  by 
fumaricand  maleic  acids,  COOH.CH  :>CH.COOH,  and 
their  halogen  derivatives,  and  by  their  honiologues  citra- 
conic  and  mesaconic  acids,  COOH.C.(CH3):  CH.COOH. 

Attempts  have  been  made  to  represent  these  differences 
by  simple  constitutional  formulae,  but  as  a  result  of  the 

1  Bischoff :  Ber.  d.  chem.  Ges.,  21,  2073. 

2  Ann.  chini   phys,,  1893. 


94  ELEMENTS   OF   STEREOCHEMISTRY 

most  rigid  investigation,  this  method  has  been  found 
incorrect,  and  one  is  led  to  the  view  that  the  one  pos- 
sibility is  to  represent  them  as  compounds  of  identical 
structure.  These  phenomena  were  designated  by  Michael 
as  alloisomerism,  and  they  led  van't  Hoff,  and  later 
L,eBel,  to  explain  them  by  stereochemical  methods. 

This  interpretation  is  to-day  generally  admitted, 
especially  since  Johannes  Wislicenus  further  investigated 
the  facts,  and  found  that  they  admitted  of  the  easy 
explanation  of  the  transition  of  one  compound  into 
another. 

b.    Determination   of    the  Configuration    of    Geometrical    Un- 
saturated  Isomers 

This  determination  rests  on  a  fundamental  hypothesis, 
viz. ,  atoms  or  groups  which  act  on  one  another  in  the 
molecule,  should  occupy  neighboring  positions. 

This  principle  is  as  important  for  the  determination 
of  stereochemical  configuration  as  the  principle 
employed  in  organic  chemistry,  to  establish  structural 
formulae  by  methods  of  substitution,  a  principle  accord- 
ing to  which  a  group  entering  a  molecule  takes  the  place 
of  that  leaving  it.  In  the  one  case  as  in  the  other,  one 
assumes  that  the  other  groups  preserve  their  relative 
positions  to  one  another. 

^-Determination  of  the  configuration  by  relations  estab- 
lished between  unsaturated  and  cyclic  compounds. — 

i.  By  transformation  of  ethylenc  into  cyclic  compounds. 
In  intramolecular  reactions  the  groups  which  unite  with 
one  another  to  form  a  closed  ring  must  be  in  close  prox- 
imity, hence  isomers  which  can  be  transformed  into  ring 
compounds  should  be  plane  symmetrical  (cis),  and  not 
central  symmetrical  (cistrans).  This  reaction  is  special 


GEOMETRICAL   ISOMKRISM  95 

to  the  oxygen  compounds,  and  really  is  found  only  in  the 
case  of  the  internal  anhydrids. 

Formation  of  anhydrids  from  unsaturated  dicarboxylic 
acids  of  the  general  formula 

RC  =  CR 

I  I 

COOH     COOH 

The  formation  of  anhydrids  is  only  effected  easily  by 
those  stereoisomers  in  which  the  two  carboxyl  groups  are 
in  close  relation.  The  axially  symmetrical  compound  in 
which  the  carboxyl  groups  are  separated  does  not  give  an 
anhydride.  This  is  shown  in  the  case  of  fumaric  and 
maleic  acids,  the  latter  only  giving  an  anhydride. 

H-C—  COOH  H—  C—  O 


H—  C—  COOH  H—  C—  CO 

Maleic  acid.  Maleic  anhydrid. 

COOH—  C—  H 

II 
H—  C—  COOH 

This  is  also  seen  with  citraconic  acid  (methyl  maleic 
acid)  and  mesaconic  acid  (methyl  fumaric  acid). 

The  unsaturated  oxy-acids  give  lactones,  thus  the  cum- 
aric  acids,  HO.C6H4.CH:CHCOOH,  can  be  represented 
by  the  following  formulae  : 

H—  C—  C6H4OH         H—  C--C6H4OH 

1.1  II 

COOH—  C—  H  H—  C—  COOH 

i.  Stable  modification.     2.  Instable  modification. 

H—  C—  C6H4 

II  >0 

H—  C-CO 

Cumaron  . 


96  ELEMENTS   OF   STEREOCHEMISTRY 

Configuration  II  represents  the  acid  which  is  trans- 
formed the  more  easily  into  the  ring  compound  by  reason 
of  the  proximity  of  the  reacting  groups.1 

2.  By  transformation  of  cyclic  into  ethylene  compounds. 
—  Inversely,  as  ethylene  plane  symmetrical  compounds 
alone  can  give  ring  compounds,  so  by  the  breaking  of  the 
ring  in  a  cyclic  compound  one  should  obtain  a  plane 
symmetrical  ethylene  compound.  Experiment  shows  that 
the  products  of  the  oxidation  of  cyclic  derivatives  are 
generally  acids  of  the  maleinoid  form.  The  following 
are  some  examples  : 

Certain  unsaturated  acids  obtained  by  the  oxidation  of 
aromatic  compounds  are  derivatives  of  maleic  acid  ;  thus 
benzene  yields  trichloracetylacrylic  acid  which  splits 
up  into  chloroform  and  maleic  acid  but  gives  no  fumaric 
acid. 

/\  CO      H 

\CH  /\/ 


/ 
\/ 


CC13    C 

"•—  ! 

CH  C 

/\ 

HOOC          H 


CO       H  HOOC 

/\/  \H 

CC13     C  C 

||        +  H20  -  CHC1,  +      || 
C  CH 

/\  / 

HOOC          H  HOOC 

The  oxidation  of  phenol  by  potassium  permanganate 
leads  to  oxalic  acid  and  inactive  tartaric  acid,3  and  this 

1  Fittig  :  Ann.  Chem.  (lyiebig),  226,  351. 

2  Carius:  Ibid.},  142,  131  ;  Kekul6  :  Ibid.,  223,  179. 

3  Dobner  :  Ber.  d.  chem.  Ges.,  24,  1755. 


GEOMETRICAL   ISOMERISM  97 

latter  must  be  considered  a  derivative  of  maleic  acid. 
( Vide  page  102).  The  action  of  chlorin  in  alkaline 
solution  on  paraamidophenol  yields  dichlormaleic  acid.1 
Resorcin  under  the  same  treatment  gives  a  dichloracetyl 
trichlorcrotonic  acid  whose  configuration  is  probably 
expressed  by  the  following  formula:2 

Cl  —  C  —  COOH 

II 
H  — C.  CC12CO.CC12H 

The  numerous  derivatives  of  pyrrhol,  of  furfuran  and 
of  thiophene  also  give  derivatives  of  maleic  acid,  while 
their  ft  methyl  compounds  are  transformed  into  deriva- 
tives of  citraconic  acid  ;3  e.g. , 

Br  —  C  —  CBr  Br  —  C  —  COOH 

I          >S     ~  || 

Br  —  C  —  CBr  Br  —  C  —  COOH 

Thiophene  tetrabromid.  Dibrommaleic  acid. 

CH3  —  C  —  CBr  CH3C  —  COOH 

|          >S     —  || 

Br  —  C  —  CBr  BrC  —  COOH 

Thiotoluene  tribromid."  Bromcitraconic  acid. 

/?.  Determination  of  the  configuration  by  relations  es- 
tablished between  ethylene  and  acetylene  derivatives. — 

i.  By  transformation  of  acetylene  derivatives  into  ethylene 
compounds. — When,  as  a  result  of  the  addition  of  atoms, 
members  of  the  acetylene  series  are  transformed  into  those 
of  the  ethylene  group,  the  elements  which  are  added 
should,  according  to  Wislicenus,  attach  themselves  to  the 
two  unsaturated  carbon  atoms,  both  on  the  same  side  of  the 

1  Zincke :  Ber.  d.  chem.  Ges.,  24,  912. 

2  Zincke  :  Ibid.,  23,  3766. 

3  Ciamician:  Acad.  L,incei,  7,  22  ;  Ber.  d.  chem.  Ges.,  24,  74  and  1347. 

7 


98  ELEMENTS   OF   STEREOCHEMISTRY 

axis  of  union.    In  this  way  one  should  obtain  plane  sym- 
metrical compounds, 

R 

C       X  R—  C—  X 

III  +    I       =  H 

C       X  R  -  C  —X 

R 

For  example,  the  tolane  dibromid  which  is  formed 
in  the  greater  proportion  on  treating  tolan  with  bromin, 
has  the  following  constitution  : 

C6H5-C-Br 

II 
C6H5—  C—  Br 

Its  isomer  has  the  axial  symmetrical  formula, 
C6H5—  C—  Br 

II 
Br-C-C6H5 

The  addition  of  hydrobromic  acid  to  phenylpropiolic 
acid, 


gives  /?-bromcinnamic  acid  represented  by  the  formula, 

C6H—  C-Br 

II 
COOH—  C—  H 

The  product  of  the  reduction  of  this  compound  is 
isocinnamic  acid,  and  not  ordinary  cinnamic  acid.  This 
method  of  formation1  and  other  facts  tend  to  prove  that 
the  cinnamic  acids  have  the  following  configuration  : 

C6H5-C-H  C6H5-C-H 

II  II 

COOH—  C—  H  H—  C—  COOH 

Isocinnamic  acid.  Cinnamic  acid. 
1  I4ebermann  :  Ber.  d.  chem.  Ges.,  35,  950. 


GEOMETRICAL   ISOMERISM  99 

Brassidic  acid  isomeric  with  erucic  acid, 

C19H39.CH  :  CHCOOH, 

should  be  plane  symmetric,1  for  it  is  produced  by  the 
reduction  of  behenoleic  acid,  C19H39.C  =  C.COOH.  The 
configuration  of  these  two  isoniers  will  then  be  : 

C19H32 — C— H  C19H39 — C — H 

II  II 

COOH— C— H  H— C— COOH 

Brassidic  acid.  Erucic  acid. 

Treated  with  bromin  or  with  hydrobromic  acid  cro- 
tonylene,  CH3C  EE  CCH3,  gives  /-brominated  derivatives 
of  plane  symmetrical  dimethyl  ethylene, 

CH3  — C  — Br  CH3  — C  — Br 

II  and  || 

CH3  — C— Br  CH3— C  — H 

These  compounds  differ  from  their  axial  symmetrical 
isomers  obtained  by  other  methods. 

2.  By  transformation  of  ethylene  into  acetylene  deriva- 
tives.— Inversely  the  formation  of  acetylene  derivatives 
by  starting  from  ethylene  compounds  should  serve  to 
indicate  the  configuration  of  the  latter. 

The  general  reaction, 

abC=Ccd  =  ac  +  l>C=Cd, 

is  not  effected  with  the  same  facility  in  the  case  of  two 
geometrical  isomers. 

If  the  groups  a  and  c  are  contiguous,  the  reaction  will 
naturally  take  place  more  readily  than  when  they  are 
axially  situated. 

Examples.— One  of  the  two  ^-chlorocrotonic  acids, 
CH3CC1 :  CHCOOH,  heated  to  70°  with  dilute  potassium 
hydroxid  solution,  is  transformed  quantitatively  into 

1  Holt :  Ber.  d.  chem.  Ges.,  25,  961. 


100  ELEMENTS   OF   STEREOCHEMISTRY 


tetrolic  acid,1  CH3C  =  C.COOH.  The  isomer  is  trans- 
formed only  at  100°  and  at  that  temperature  even,  the 
change  is  but  partial.  These  reactions  are  expressed  by 
the  following  scheme  : 

CH3  Cl  —  C—  CH3 

C1  —  C  —  CH3  easily  C 

||  HI       difficultly 

H  —  C  —  COOH  C  COOH  —  C  —  H 

COOH 

The  two  stereoisomeric  monohalogen  propylenes, 
CH3CH  =s=  CHX,  present  the  same  peculiarity.  They 
are  prepared  by  starting  from  .the  dihalogen  butyric  acids 
(formed  by  the  addition  of  bromin  or  chlorin  to  the 
Stereoisomeric  crotonic  acids  )  according  to  the  following 
equation  : 

CH3.CHX.CHX.COONA  = 

NaX  +  C02  -f  CH3.CH.CHX. 

By  elimination  of  hydrochloric  acid  one  of  the 
isomers  gives  allylene,  CH3C  ==  CH,  easily,  the  other  with 
difficulty, 

CH3  —  C  —  H  CH3  —  C  —  H 

|  and  || 

H  —  C  —  X  X  —  C  —  X* 

y.  Determination  of  configuration  by  relations  estab- 
lished between  saturated  and  unsaturated  compounds. 

i.  By  transformation  of  ethylene  derivatives  into  satu- 
rated  compounds.  —  When  an  unsaturated  compound  is 
transformed  by  addition  into  a  saturated  compound  of 
symmetrical  structure,  and  with  two  asymmetric  carbon 
atoms, 

1  Friedrich  :  Ann.  Chem.  (I^iebig),  219,  361. 

2  Wislicenus  :  Ibid.,  248,  279. 


GEOMETRIC AI<   ISOMERISM  IOI 

abC=Cab  -\-cc=  abcC—Cabc, 

the  product  obtained  is  either  by  extra-  or  intramolecular 
compensation  always  inactive.  The  following  particu- 
larly important  example  shows  that  a  plane  symmetrical 
ethylene  derivative  produces  a  non-racemic  compound, 
while  an  axial  compound  gives  a  derivative  which 
cannot  be  separated  into  optical  isomers.1  It  was  known 
for  some  time  that  maleic  acid2  on  oxidation  with  potas- 
sium permanganate  is  transformed  into  a  non-cleavable 
tartaric  acid,  while  fumaric  acid3  under  the  same  con- 
ditions, yields  racemic  acid, 

COOHCH  :  CHCOOH  +  H2O  +  O  = 

COOH.CH(OH).CH(OH).COOH. 

It  would  be  impossible  by  ordinary  methods  to  say 
which  inactive  tartaric  acid  is  produced,  according  as 
fumaric  or  maleic  acid  is  used.  By  considering  the 
phenomenon  from  a  stereochemical  standpoint,  the 
reactions  must  necessarily  take  place  in  the  way  that 
actual  experimental  results  have  shown. 

OH 
H  — C  —  COOH       OH  H  — CHCOOH 

ii  +  r 

H  — C  —  COOH       OH  H  — C  —  COOH 


.An 


Maleic  acid.  Inactive  tartaric  acid. 

1  I^eBel:  Bull  Soc.  Chim.  (2),  37,  300;  Wislicenus,  Konigl.  Sachs  Gesell. 
d.  Wissenschaft,  14. 

2  Kekul£  and  Anschiitz  :  Ber.  d.chem.  Ges.,  14,  713. 

3  Kekul£  and  Anschiitz  :  Ibid.,  13,  2150. 


102  ELEMENTS   OF   STEREOCHEMISTRY 

OH 

COOH  —  C  —  H       OH  COOH  —  C— H 

II  +  I 

COOH  — C  — H       OH  COOH  — C  — H 


Maleic  acid. 


H  — C  — COOH  OH 

I!  + 

COOH  —  C  —  H          OH 


OH 

Inactive  tartaric  acid. 

OH 
H— C  — COOH 

I 
COOH  —  C  —  H 

OH 


COOCHC  — H 


OH 

II  -f 

HC  — COOH  OH 


Dextrotartaric  acid,    f  8 
OH 

COOHC— H 

HC— COOH 

Laevotartaric. 


2.  By  relations  between  saturated  compounds  and  sub- 
stances belonging  to  the  ethylene  group. — If  it  be  assumed, 
as  was  done  by  Wislicenus,  that  saturated  compounds  are 
characterized  by  a  certain  configuration,  more  or  less 
advantageous,  one  may  easily  account,  for  example,  for 
the  formation  of  the  dibromid  of  tolane  by  simple 
elimination  of  bromin  from  the  tetrabromid,  and  in  the 
same  way  may  be  explained  the  formation  of  fumaric 
acid  by  the  dehydration  of  malic  acid.  The  different 
configurations,  and  at  the  same  time  the  intramolecular 
attractive  forces  of  the  component  groups  of  tolane 
tetrabromid,  and  of  malic  acid,  are  expressed  by  the 
following  formulae  : 


GEOMETRICAL   ISOMERISM  103 

Br  Br 

I  I 

C6H5.C.Br  C6H5.C-Br 

C6H5.C.Br  Br.C.C6H5 

Br  Br 

Disadvantageous.  Advantageous. 

OH          OH  OH 

COOH—  C—  H   COOH.C—  H    COOH—  C.H 

!        I          I 

COOH—  C—  H       HC—  H         HC—  COOH 

I  I  I 

H  COOH  H 

Disadvantageous.         More  advantageous.     Most  advantageous. 

The  reactions  which  are  expressed  by  the  equations, 
C6H5.CBr2.CBr2C6H5  -  C6H5.CBr  :  CBr.C6H5  +  Br2, 
COOH.CH(OH).CH2COOH  = 

COOH  CH  :  CHCOOH  +  H2O, 

are  to  be  explained  principally,  or  even  exclusively,  by 
assuming  certain  advantageous  configurations.  It  is 
then  necessary  to  assume  that  there  is  a  predominant 
formation  of  axial  symmetrical  tolane  dibromid,  and  of 
fumaric  acid. 

Br 


C6H5.C.Br  Br 

ii  i      i 

BrCCH          Br 


OH 
COOH.C.H  COOH.  C.H  OH 

I  =  II  +1 

H.C.COOH  H.C.COOH       H 

H 


104  ELEMENTS   OF   STEREOCHEMISTRY 

In  some  cases  the  configurations  of  the  saturated  com- 
pound and  of  the  unsaturated,  which  is  derived  from  it, 
are  determined  by  the  fact  that  the  elements  eliminated, 
in  order  to  pass  from  one  to  the  other,  must  necessarily 
occupy  neighboring  positions.  It  is  thus  that  dibrom- 
succinic  acid,  a  substance  analogous  to  inactive  tartaric 
acid,  can  lose  a  molecule  of  HBr  only  when  an  atom  of 
hydrogen  is  placed  in  contiguity  with  an  atom  of  bromin. 
It  must  follow  then,  that  the  acid  so  yielded  is  brom- 
fumaric  acid  and  not  brommaleic  acid. 

<5.  Determination  of  the  configuration  by  relations 
established  between  ethylene  derivatives. — Considerations 
analogous  to  the  preceding,  permit  a  much  easier  expla- 
nation of  the  passage  from  axial  symmetrical  to  axial 
symmetrical  isomers.  It  suffices  to  admit  the  formation 
of  an  intermediate  saturated  derivative,  and  to  take  into 
account  an  advantageous  configuration  which  it  will 
assume  during  the  reaction. 

As  examples,  will  be  taken  the  reciprocal  trans- 
formations of  unsaturated  dibasic  acids.  These  reactions 
take  place  in  the  presence  of  a  small  quantity  of  bromin, 
or  of  hydrobromic  acid,  thus  : 

C2H2(COOH)2  +  Br2  =  C2H2Br2(COOH)2. 
C2H,Br(COOH)2  =  C2HBr(COOH)2+  HBr. 

In  this  case  fumaric  acid  gives  brommaleic  acid  and 
maleic  acid  bromfumaric  acid. 

If  one  gives  to  maleic  acid  a  plane  symmetrical  formula 
and  an  axial  symmetrical  formula  to  fumaric  acid,  these 
transformations  may  be  expressed  in  the  following 
manner  : 


GEOMETRICAL  ISOMERISM  105 

Br 
COOH  —  C—H  Br  COOH  — C 


H.C.i 


H.C.COOH       Br  H.C.COOH     -~ 

Br 

Fumaric  acid.  Disadvantageous  position 

Rotation.  of  dibromsuccinic  acid. 


Br 
COOH.C.H  Br      COOH  — C  —  H 

"~*  I          ==      I  "f 

COOHC.Br  H  COOH.C.Br 

H 

Advantageous  configuration  of 

dibromsuccinic  acid.  Maleic  acid. 


Br 
COOH. C  —  H       Br  COOH.C.H 

II  +   I      ==  I      — 

COOHCH  Br  COOH.C.H 

Br 

Maleic  acid.  Disadvantageous  configuration. 

Rotation. 

Br 
COOH.C.H  H        COOH.C.H 

I  =     !    +  II 

Br.C.COOH  Br  BrC.COOH 

H 

Bromfumaric  acid. 

These  phenomena  are  to  be  found  in  some  stereo- 
isomeric  monobasic  acids  also,  viz. ,  the  isomeric 
brassidic  and  erucic  acids,  C19H39.CH=CH.COOH. 


106 


ELEMENTS   OF   STEREOCHEMISTRY 


The  stereochemical  formulae  given  on  page  99  alone 
permit  the  explanation  of  the  decomposition  of  dibrom- 
brassidic  acid  into  hydrobromic  acid  and  monobrom- 
erucic  acid,  and  the  similar  transformation  of  dibrom- 
erucic  acid  into  monobrombrassidic  acid.1 


C19H39.C.H 


COOH—  C.H 
Brassidic  acid. 

Br  Br 

C19H39.C.H      C19H39.C.H 

|    —  | 

COOHC.H  HC.Br 

Br  COOH 

Dibrombrassidic  acid. 

C19H39.C.H 

II 

H.C.COOH 
Erucic  acid. 


+ 


Br 
Br 


H 

=    |      + 
Br 


Br 

Br 


C19H39.C.Br 


H.C.COOH 

Bromerucic  acid. 


Br     • 
C19H39.C.H  ^ 

H.C.COOH 

Br 
Dibromerucic  acid. 


Br 


C19H39.C.H 


C19H39CBr 


H 

COOHCBr         Br       COOH  C  H 
H 

Brombrassidic  acid. 


By  replacement  of  the  bromin  by  hydrogen,  one 
absolutely  proves  the  reciprocal  transformation  of  the 
two  acids.  The  above  formulae  also  tend  to  show  that 
brombrassidic  acid  should  be  transformed  more  easily 
than  its  isomer,  an  assumption  which  is  supported  by 
experiment. 

1  Holt  :  Ber.  d.  chem.  Ges.,  24,  4120. 


GEOMETRICAL   ISOMERISM  1 07 

Angelic  and  tiglic  acids,  the  1.2  dimethyl  acrylic  acids, 
CH3.CH.CCH3.COOH,  should  be  represented  by  the 
following  formulae  : 

CH,~C— H  CH3.C.H 

II  and  || 

CH3C— COOH  COOH.C.CH3 

Angelic  acid.  Tiglic  acid. 

for  their  dibrom  derivatives,  CH3.CHBr.C(CH3)Br- 
COOH,  heated  with  sodium  carbonate  give  two  different 
monobrompseudobutylenes, 

CH3CHBrC(CH3)BrCOONa  = 

NaBr  +  CO2  +  CH3.CH  :  C(CH3)Br.1 

The  monobrompseudobutylene  derived  from  tiglic 
acid  is  the  substance  described  as  crotonolyene  hydro- 
bromide,  as  it  is  more  easily  transformed  into  crotonylene 
than  the  isomer  derived  from  angelic  acid. 

It  is  necessary  to  assume  that  sodium  salts  of  the 
dihalogen  acids  react  with  evolution  of  carbon  dioxid 
and  that  in  consequence  the  groups  Br  and  COONa  were 
originally  in  neighboring  advantageous  positions. 

Uncertainty  in  the  determination  of  configuration. — The 
different  methods  employed  to  determine  configurations 
although  giving  in  most  instances  good  results,  always, 
present  an  element  of  uncertainty.  The  principle  of 
advantageous  configuration  of  the  intermediate  deriva- 
tives, as  the  name  itself  indicates,  is  a  somewhat  vague 
conception  which  is  difficult  to  bring  into  a  more  precise 
view  by  reason  of  the  insufficiency  of  our  knowledge 
regarding  affinity. 

As  a  matter  of  fact  the  affinities  which  are  brought 
into  play  in  the  molecule  itself  should  be  influenced,  and 
often  modified  either  by  external  conditions,  such  as 

1  Wislicenus  :  Ann.  Chem.  (I^iebig),  250,  224. 


108  ELEMENTS   OF   STEREOCHEMISTRY 

temperature,  or  by  such  chemical  reagents  as  the  solvents 
in  which  the  reaction  takes  place,  or  certain  substances  in 
solution  which  start  the  reaction.  As  an  example  of  the 
last  mentioned  may  be  taken  the  varying  influence  of 
different  dehydrating  agents.  Frequently  also,  secondary 
reactions  take  place  of  such  a  kind  that  often  the  reaction 
cannot  be  assumed  to  be  as  simple  as  the  ordinary  equa- 
tion indicates.1  Finally,  all  these  methods  presuppose 
that  the  groups  which  take  part  in  the  reaction  are  not 
otherwise  modified  by  these  transformations.  This 
method  of  reasoning  is,  then,  not  applicable  in  those 
cases  where  intramolecular  transpositions  take  place, 
and  these  reactions  are  much  more  frequent  in  stereo- 
isomeric  reactions,  particularly  in  those  in  which  geo- 
metrical isomers  take  part.  It  is  then  necessary  to 
strictly  define  the  conditions  which  are  necessary  to  the 
explanation  of  these  cases. 

c.    Changes   in  Configuration  of  Geometrical  Isomers  of  the 
Ethylene  Group 

a.  With  change  of  constitution. — The  transformation  of 
geometrical  isomers,  one  into  the  other,  can  be  regarded 
as  a  change  in  configuration  following  an  intramolecular 
decomposition,  a  phenomenon  which,  as  a  rule,  is  favored 
by  an  elevation  of  temperature. 

Hence  it  is  that  the  atomic  grouping  which  is  the 
more  stable  under  the  conditions  of  experiment  shows  a 
tendency  to  re-formation.  Thus,  the  same  maleic  anhy- 
drid  is  always  formed,  whether  one  distils  the  maleic 
acid  or  fumaric  acid. 

/?.  Direct  transformation  without  change  of  constitution. 
— These  reactions  are  characteristic  of  geometrical  isomers. 

1  Wislicenus  :  Ann.  Chem.  (lyiebig),  246,  53  ;  248,  353. 


GEOMETRICAL   ISOMERISM  IO9 

In  contradistinction  to  optical  isoniers,  Cabcd,  two 
geometrical  isomers,  abC=Ccd,  cannot  have  the  same 
stability.  The  stability  here  depends  on  many  factors, 
and  if,  for  example,  the  affinity  of  a  for  <:,  and  b  for  d 
on  the  one  hand,  are  stronger  than  those  of  a  for  d,  and 
b  for  c  on  the  other,  the  stable  and  unstable  configurations 
will  be  represented  by  the  following  formulae  : 

a—£—b  a—C—d 

II  II 

c—  C— d  d—C—c 

Stable.  Unstable. 

The  different  stabilities  of  geometrical  isomers  corre- 
spond also  to  the  different  heats  of  combustion  which  are 
thermochemical  measures  of  the  stability  of  these  com- 
pounds. Thus  stable  fumaric  acid  develops  319  calories 
on  combustion,  whereas  the  unstable  maleic  acid  gives 
326.3  calories.1  The  transformation  of  maleic  acid  into 
fumaric  acid  is  an  exothermic  phenomenon  which  can 
therefore  be  effected  without  the  intervention  of  any 
extraneous  energy.  Consequently  geometrical  isomers 
have  a  tendency  to  the  formation  of  the  more  stable 
compound,  and  not,  as  in  the  case  of  optical  isomers,  to 
the  formation  of  a  mixture  of  the  two  substances  in 
equimolecular  proportions. 

This  explains  why  in  the  case  of  the  two  butylene, 
for  example,  one  has  not  been  able  to  isolate  the  two 
isomers.  It  is,  perhaps,  well  to  point  out  that  all  the 
considerations  given  above  are  quite  independent  of  any 
conception  regarding  intramolecular  movement. 

Transformation  of  geometrical  isomers  of  the  ethylene 
series  under  the  influence  of  heat. — This  kind  of  trans- 
formation is  quite  general  and  in  most  cases  non- 

1  Stohmann:  J.  prakt.  Chem.,  41,  575. 


110  ELEMENTS   OF   STEREOCHEMISTRY 

reversible.  As  examples  may  be  cited :  maleic  acid 
unstable  as  such,  but  stable  in  the  form  of  an  anhydrid 
heated  to  150°  is  transformed  nearly  quantitatively  into 
fumaric  acid  ;  and  the  transformation  of  isocinnamic  acid 
into  ordinary  cinnamic  acid,  etc.  This  does  not  occur 
when  the  two  isomers  have  nearly  the  same  stability.  In 
these  cases  the  reaction  may  be  reversible,  and  although 
one  may  submit  the  compounds  to  the  action  of  heat  a 
mixture  of  the  two  substances  is  obtained  which  is, 
however,  seldom  equimolecular.  Thus  it  is  that  on  heat- 
ing the  dibromids  or  dichlorids  of  tolane,  a  mixture  of 
the  two  compounds 

C6H6— C— Cl(Br)         C6H6— C— Cl(Br) 

C6H5— C--C1  ( Br )          ( Br  ( Cl— C— C6H5 

Unstable.  Stable. 

is  obtained  in  which  the  stable  modification  exists  in  a 
larger  proportion.  As  might  be  expected  this  state  of 
equilibrium  is  reached  more  easily  by  starting  from  the 
unstable  plane  symmetrical  compound  than  by  using  the 
more  stable  axial  symmetrical  isomer. 

Transformations  of  this  kind  can  even  be  utilized  to 
determine  the  relative  stability  of  two  geometrical 
isomers  by  investigating  the  composition  of  the  resulting 
mixture,  and  the  rapidity  with  which  the  reversible 
reaction  takes  place.  In  this  way  the  constitution  of  the 
OL-  and  yft-chlorocrotonic  acids  has  been  established. 

tf-Chlorocrotonic  acids. 
CH3  —  C  —  H  CH3  —  C  —  H 

II  II 

COOH  —  C  —  Cl  Cl  —  C  —  COOH 

More  stable.  Less  stable. 


GEOMETRICAL   ISOMERISM  III 

/?-Chlorocrotonic  acids. 
CH3— C— Cl  CH3— C-C1 

II  II 

H  C— COOH  COOH  C— H 

More  stable.  Less  stable. 

Spontaneous  transformation  of  isomeric  ethylene  deriv- 
atives in  the  presence  of  certain  substances. — Elevation  of 
temperature,  as  has  been  seen,  has  a  tendency  to  produce 
molecular  transformation.  An  interesting  phenomenon, 
and  one  which  is  much  more  difficult  of  explanation,  is 
the  same  reaction  produced  by  the  simple  presence  of 
certain  substances. 

In  these  cases  it  is  observed  that  unstable  modifications 
suffer  transition  into  their  more  stable  isomers  in  the 
presence  of  substances  which  apparently  take  no  part  in 
the  reaction. 

Bromin  and  certain  mineral  acids1  convert  maleic  acid 
into  fumaric  acid  ;  this  reaction  is  more  or  less  rapid  and 
complete  according  to  the  reagent  employed,  and  the 
temperature  at  which  the  experiment  is  made.  The  same 
reaction  takes  place  with  the  salts  of  maleic  acid,  and  in 
this  case  it  appears  to  depend  on  the  character  of  the 
metallic  base.2  Mere  traces  of  iodin  suffice  to  convert 
the  maleic  esters  into  the  fumaroid  form  ;3  traces  of  nitrous 
acid  induce  the  transformation  of  oleic,  hytogeic,  and 
erucic  acids  into  their  stereoisomers,  -elaidic,  gaidic,  and 
brassidic  acids  as  the  following  scheme  indicates  : 

C«H2,Z  + 1— C  —  H  CnH2— C  —  Hw  + 

li  —  II 

COOH  — C  — H  H  — C  — COOH 

1  Petrie  :  Ann.  Chem.    (I,iebig),   195,59;  Kekule:  Ann.  spl.   i,  134;  Ibid. 
2,  93  and  6. 

2  Skraup  :  Wiener  Monatshefte,  12,  107. 

3  Anschiitz  :  Ber.  d.  chem.  Ges.,  12,  2282. 


I 
112  ELEMENTS   OF   STEREOCHEMISTRY 

Amidomaleic  acid1  and  anilidomaleic  acid  when 
heated  with  alkalies  give  fumaric  acid,  and  the  citraconic 
acid  derivatives  give  mesaconic  acid.  The  latter  reaction 
although  incomplete  is  not  reversible ;  equilibrium  is 
reached  when  the  mixture  contains  70  per  cent,  of  the 
mesaconic  acid  derivative,  and  30  per  cent,  of  the  citra- 
conic derivative.  It  is  here  seen  that  the  salts  of  the 
acids  are  more  apt  to  produce  these  molecular  changes  ; 
the  presence  of  a  methyl  group  seems  to  be  more  favor- 
able to  this  end  than  others.2 

Difficulties  in  the  determination  of  configuration  in  the 
case  of  spontaneous  molecular  transformations. — These 
changes  due  to  the  presence  of  an  apparently  indifferent 
body,  and  which  can  be  compared  to  catalytic  reactions 
complicate  an  exact  determination  of  configuration ,  and ,  ex  • 
plain  why  one  is  led  in  some  cases  to  contradictory  results. 

It  has  been  seen  that  by  means  of  addition,  one  should 
obtain  from  acetylene  derivatives,  plane  symmetrical 
ethylene  compounds,  but  there  is  always  yielded  a  certain 
amount  of  the  cistrans  compound,  the  presence  of  which 
can  easily  lead  to  an  error  in  the  determination  of  the 
configuration. 

Acetylene  dicarboxylic  acid,  COOH— C  =  C— COOH, 
treated  with  bromin,  gives  but  30  per  cent,  dibrom- 
maleic  acid  and  70  per  cent,  dibromfumaric  acid.3 
Phenylpropiolic  acid,  submitted  to  the  same  treatment, 
yields  a  mixture  of  two  dibromcinnamic  acids.4  The 
analogous  dichlorcinnamic  acid  leads  by  reduction  not  to 
isocinnamic  acid,  but  to  ordinary  cinnamic  acid.5 

1  Anschiitz  :  Ann.  Chem.  (I^iebig),  259,  138. 

2  Delisle:  Ibid.,  269,  95. 

3  Michael :  J.  prakt.  chem.,  46,  209. 

*  Roser :  Ann.  Chem.  (Liebig),  247,  139. 
5  Niessen  :  Ber.  d.  chem.  Ges.,  25,  2666. 


GEOMETRICAL   ISOMERISM  113 

In  all  these  cases  phenomena  of  addition  are  accom- 
panied or  even  hidden  by  molecular  transposition,  in 
which  the  substance  which  should  normally  be  produced 
is  converted,  more  or  less,  into  its  more  stable  isomer, 
the  reaction  tending  finally  to  a  state  of  equilibrium.  One 
can  easily  conceive  that  these  transformations  can  be 
favored  by  the  presence  of  extraneous  substances  or  by 
the  disengagement  of  heat  produced  in  the  reaction. 

The  number  of  these  abnormal  cases  will  certainly 
decrease  when  the  conditions  under  which  the  different 
isomers  can  exist  unaltered  is  known. 

Wislicenus  has  proved  that  angelic  and  tiglic  acids 
give  their  respective  dibromo  compounds  quantitatively 
only,  when  one  allows  the  reaction  to  proceed  in  the 
presence  of  a  large  excess  of  bromin  at  a  low  tempera- 
ture, and  in  the  absence  of  light.  If  one  operates  under 
other  conditions,  a  certain  amount  of  the  stereoisomers 
is  always  formed.  It  must  be  noted  that  it  is  not  the 
dibromo  compounds  which  submit  to  the  transformation, 
but  the  acids  themselves,  during  the  progress  of  the 
bromination.  Finally,  as  one  might  expect,  the  unstable 
angelic  acid  gives  a  much  larger  quantity  of  dibrom- 
tiglic  acid  than  does  tiglic  acid,  dibromangelic  acid.1 

Attempts  to  interpret  the  phenomena  of  molecular  trans- 
position.— Wislicenus  wras  the  first  to  attempt  to  give  an 
explanation  of  the  spontaneous  transformation  of  the 
geometric  isomers  of  ethylene  produced  by  contact  action  ; 
he  applied  himself  for  the  most  part  to  the  cases  detailed 
on  page  93,  which  are  accomplished  with  changes  of  con- 
stitution, and  on  the  other  hand  to  the  transformation  of 
certain  structural  isomers,  such  as  the  passage  of  primary 
propyl  derivatives  to  those  of  the  secondary  structure. 

1  Wislicenus  :  Ann.  Chem.  (I^iebig),  272,  i. 
8 


114  ELEMENTS   OF   STEREOCHEMISTRY 

According  to  Wislicenus  the  body  acting  purely  cata- 
lytically  should  give  an  addition  product  with  the  ethy- 
lene  compound ;  this  product  should  follow  the  more 
favorable  configuration,  and  under  this  form  the  sub- 
sequent separation  of  the  elements  added  would  take 
place  with  the  formation  of  an  unsaturated  compound  of 
the  same  constitution  but  with  a  different  configuration  ; 
or  in  other  words  a  stereoisomer  of  the  original  body. 

In  this  way  the  substance  which  acted  apparently 
catalytically  would  be  continuously  regenerated  to  enter 
anew  into  the  reaction. 

Thus  the  transformation  of  maleic  acid  to  fumaric  acid 
should  take  place  with  the  intermediate  formation  of 
chlorsuccinic  acid  according  to  the  following  configura- 
tions : 

H" 
COOH.C.H'       H"  COOH.C.H' 

II         +    I  I  — 

COOH.C.H         Cl  COOH.C.H 

Cl 
If 

H— C— COOH 

H"— C— COOH       H' 

COOH.C.H  ||  -4-    | 

Ci  COOH.CH  Cl 

This  explanation  must  be  taken  with  certain  reserva- 
tions, for  in  most  cases  it  is  not  possible  to  isolate  the 
intermediate  substance  which  one  is  compelled  to  assume, 
even  in  traces  ;  and  when  one  performs  the  reaction  in 
another  way  the  transformation  does  not  take  place  as 
the  explanation  of  Wislicenus  would  indicate.  As  an 
example  of  this,  one  may  cite  the  case  of  chlorsuccinic 


GEOMETRICAL   ISOMERISM  115 

acid  which  does  not  give  f umaric  acid  under  the  condition 
that  one  starts  from  maleic  acid  in  the  presence  of  hydro- 
chloric acid.  Moreover,  it  is  difficult  to  understand  how 
molecular  transpositions  are  effected  by  the  agency  of 
heat  alone  without  the  intervention  of  an  indifferent 
substance  and  the  consequent  formation  of  an  unstable 
addition  product. 


According  to  the  notion  which  one  usually  has  of 
valence,  it  is  necessary  to  admit  that  the  two  groups  a 
and  b  corresponding  to  the  letters  in  Fig.  15,  change 
place,  which  is  altogether  improbable,  especially  where 
one  of  the  linkages  of  the  double  bond  is  broken 
momentarily,  and  these  then  revolve  through  an  arc  of 
1 80°  in  order  to  reunite.  All  these  difficulties  which  are 
analogous  to  those  encountered  in  the  consideration  of 
the  relation  of  an  active  substance  to  its  optical  isomer 
disappear  if  one  will  partly  abandon  the  idea  of  valence 
as  Werner  has  done.1  According  to  him  there  are  no 
single,  double,  or  triple  linkages  between  the  atoms.  A 
system  such  as  abC  Cab  is  stable  only  on  condition  that 

1  Beitrage  zur  Theorie  der  Affinitat  und  Valenz,  p.  16. 


u6 


ELEMENTS   OF   STEREOCHEMISTRY 


the  change  of  affinities  (as  has  already  been  defined  on 
page  87)  is  at  a  maximum.  A  system  of  this  kind  will 
present  two  forms  satisfying  this  condition  (Fig  16, 
rings  i  and  2). 


Fig.  16. 

In  these  figures  the  zones  not  covered  by  shading  are 
those  in  which  the  affinities  or  attractions  are  saturated 
by  the  four  groups,  a,  a,  b,  b;  the  shaded  parts  are  those 
in  which  the  affinities  serve  to  link  together  the  two 
atoms  of  carbon. 

So  that  in  these  last  mentioned  cases  the  parts  X1  (ring 
3),  are  saturated  under  all  circumstances,  as  completely 
in  compounds  having  a  single  linkage,  as  in  those  with  a 
double  bond,  whilst  the  parts  X2  which  react  one  on 
another  and  belong  to  the  system  abC  caE  have  the 
effect  of  preventing  the  free  rotation  of  two  atoms  of 
carbon  round  a  common  axis.  It  is  this  which  renders 
two  stable  configurations  possible.  Or  stated  more 
simply,  if  one  body  passes  easily  from  one  to  another  of 
these  configurations,  it  is  because  the  affinities  changed 


GEOMETRICAL   ISOMERISM  1 17 

between  the  zones  X2,  which  are  certainly  feeble,  can  be 
rendered  still  more  feeble,  either  by  molecular  concus- 
sions which  are  exercised  on  these  zones  in  certain  sub- 
stances, which  is  particularly  the  case  in  dealing  with 
free  ions.  When  one  has  a  case  of  this  kind,  the  two 
atoms  of  carbon  take  up  again  their  oscillatory  power 
round  their  axis  of  union,  and  the  unstable  molecule 
returns  directly  to  a  stable  type  without  the  necessity  of 
supposing  the  formation  of  an  intermediary  compound. 

Configuration  of  ethylene  compound  of  which  the  two 
geometric  isomers  are  not  known. — We  have  already 
seen  (page  109)  that  even  in  certain  very  simple  cases  the 
two  geometric  isomers  have  not  as  yet  been  isolated.  For 
example,  one  only  knows  of  but  one  dihalogen  or  dialkyl 
derivative  of  ethylene  and  the  same  is  true  for  stilbene. 

Among  the  unsaturated  dicarboxylic  acids  one  knows, 
on  the  one  hand,  the  fumaricand  maleic  acids,  and  on  the 
other  hand,  the  mesaconic  and  citraconic  acids,  but  the 
dicarboxylic  acid,  and  particularly  the  diphenyl  acids 
have  not  yet  been  isolated  in  the  two  isomeric  formations 
despite  the  numerous  efforts  that  have  been  made  in  this 
direction. 

The  configuration    of   the   dihalogen    derivatives   of 
ethylene  should  be  centro-symmetric  by  reason  of  the 
great  affinity  of  chlorin  for  hydrogen, 
Cl— C— H 

li 
H— C— Cl 

whilst  the  plane  symmetric  isomer 
Cl— C— H 

II 
Cl— C— H 

is  probably  too  unstable  to  be  isolated. 


Il8  ELEMENTS   OF   STEREOCHEMISTRY 

There  can  be  no  doubt  regarding  the  configuration  of 
the  dissociated  dicarboxylic  acids,  for  they  correspond  in 
their  properties  very  closely  to  maleic  acid,  particularly 
in  the  ease  with  which  they  give  an  anhydrid  from 
which  the  name  maleinoid  has  been  given  to  them  in 
contradistinction  to  the  less  stable  fumaroid  type  which 
corresponds  to  fumaric  acid  ;  thus,  the  acid 

—  C—  COOH 


—  COOH 
is  well  known,  while  the  isomer 

—  COOH 


COOH— 

has  not  been  obtained.  For  reasons  which  are  still 
unknown,  the  presence  of  hydrocarbon  radicals  favors 
the  plane  symmetric  configuration.  This  affords  a  striking 
example  of  the  influence  of  constitution  on  configurations. 
Moreover,  although  it  is  not  always  possible  to  isolate  the 
two  geometric  isomers,  their  existence  may  be  established 
by  indirect  proof.  For  example,  pyrocinchonic  (dimethyl 
maleic)  acid  gives,  on  reduction  in  alkaline  media,  not 
only  non-racemic  dimethylsuccinic  acid,  which  should  be 
formed  according  to  the  equation,  but  also  the  racemic 
dimethylsuccinic  acid  (page  53).  It  is  necessary  on  this 
account  to  admit,  as  in  the  case  of  the  partial  trans- 
formation of  citraconic  acid  into  mesaconic  acid,  that  there 
is  formed  by  intramolecular  transposition  a  salt  of 
dimethylfumaric  acid,  which  alone  can  produce  the  second 
racemic  dimethyl  fumaric  acid. 

II.  STEREOCHEMISTRY  OF  SATURATED 
COMPOUNDS 

It  may  have  already  been  remarked  that  the  stereo- 


GEOMETRIC AI,   ISOMKRISM  119 

chemistry  of  the  derivatives  of  methane  is  not  strictly 
comparable  in  all  points  with  that  of  the  ethylene  com- 
pounds. By  reason  of  the  law  of  mobile  union,  the  dif- 
ferent configurations  should  be  viewed  as  forms  which 
are  more  or  less  stable  corresponding  to  different  phases 
of  intramolecular  movements.  The  fact  that  two 
unsaturated  geometric  isomers  lead  in  certain  cases  to  one 
and  the  same  saturated  compound,  in  particular  the  fact 
that  the  reduction  of  f umaric  and  maleic  acids  performed 
with  the  greatest  care  lead  always  to  the  same  succinic 
acid,  forces  one  to  conclude  that  in  the  two  configura- 

H  H 

H— C— COOH  H— C— COOH 

I  i 

H— C— COOH        COOH— C— H 

H  | 

H 

tions,  the  maleinoid  configuration  is  transformed  probably 
spontaneously  by  rotation  into  the  more  advantageous 
fumaroid  configuration.  Thus  it  would  not  be  contrary 
to  theory  to  say  that  in  certain  cases  these  different 
phases  of  intratomic  movement  represent  positions  of 
relatively  stable  equilibrium,  but  it  is  evident  that  they 
are  transformed  exceedingly  easily  one  into  the  other, 
and  would  correspond  closely  to  the  idea  that  one  has  in 
the  term  ' '  modification  ' '  more  than-  to  a  true  isomer. 
It  is  possible  that  the  two  characteristic  forms  of  dibrom- 
propionic  acids,  of  monochloracetic  acid,  and  the  three 
modifications  of  phenylhydrocinnamic  acid  may  be  looked 
upon  as  belonging  to  this  category. 

a.  Determination  of  the  position  of  advantage  or  of 
unstable  position. — This  determination  which  is  of  great 


120  ELEMENTS   OF   STEREOCHEMISTRY 

importance  in  the  stereochemistry  of  saturated  com- 
pounds has  been  studied  in  detail  in  the  case  of  dibasic 
acid  by  Auwers,  V.  Meyer,  and  others,  particularly  by 
Bischoff .  Succinic  acid  which  yields  an  anhydrid  with 
difficulty,  that  is,  it  has  a  weak  affinity  constant1 
(fc  =  0.0068),  corresponds  in  its  properties  to  fumaric 
acid.  In  its  stable  configuration  the  two  carboxyl  groups 
should  be  opposed  to  one  another  or  could  even  be  in  an 
intermediary  position  between  the  two  hydrogen  atoms 
of  the  other  CH2  group.  It  is  thus  necessary  to  assign 
to  it  symbol  i  in  Fig.  17.  Succinic  anhydrid,  on  the 


COOH 


COOH 


Fig.  17. 

other  hand,  which  corresponds  to  the  maleinoid  type 
should  be  represented  by  symbol  2  in  Fig.  17,  these  two 
types  being  viewed  in  the  direction  of  the  axis  which 
joins  the  two  carbons  CH2 — CH2. 

1  According  to  Arrhenius  all  electrolytes  in  aqueous  solution  are  more  or 
less  dissociated  into  their  ions.  The  electrical  conductivity  which  depends  on 
dissociation  increases  with  increasing  dilutions  and  tends  to  become  constant 
and  reaches  a  maximum  with  very  weak  solution.  It  denotes  the  molecular 
conductivity  with  weak  solutions  and  in  the  same  constant  for  a  solution  con- 
taining i  gram  molecule  in  V  liters,  the  relation  a  =-  —  represents  the  degree 
of  dissociation.  This  quantity  varies  with  the  dilution.  So  that  one  may 
express  it  by  the  following  formula  given  by  Ostwqld  : 


V(I— a) 

k   is  a  constant  which  for  the   same  acid  and  particularly  for  monobasic 
acids  preserves  the  same  value  in  all  dilutions.     This  constant  varies  with 


GEOMETRICAL   ISOMERISM  121 

In  the  same  way  that  the  unsaturated  acid  is  only 
known  in  the  maleinoid  form  and  gives  spontaneously  an 
anhydrid,  so  in  the  alkylsuccinic  acids  the  fumaroid 
character  disappears  little  by  little  to  be  replaced  by  a 
maleinoid  property  according  as  the  number  of  alkyl 
radicals  increase  ;  in  other  words  the  acids  tend  to  become 
stronger2  and  have  a  greater  tendency  besides  to  give  an 
anhydrid.  It  is  thus  necessary  to  conclude  that  the 
carboxyl  groups  are  coming  closer  together.  The 
maleinoid  type  is  stable  only  in  tri-  and  tetramethyl 
ethylene  (Fig.  18) ,  which  ire  however  transformed  almost 

CH3 


COOH 


COOH 


spontaneously  into  an  anhydrid. 

Relations  of  the  same  kind  exist  between  the  glutaric, 
adipic,  and  pimelinic  acids  and  their  alkyl  derivatives. 
For  example,  may  be  cited  levulinic  acid,  CH3.CO. 

different  acids  and  appears  to  be  directly  dependent  on  the  constitution  ;  thus 

one  finds  for  the  chlorbenzoic  acids 

Parachlorbenzoic  acid,  k  =  0.132 

Metachlorbenzoic  acid,  k  =  0.0155 

Parachlorbenzoic  acid,  k  =  0.0093 

lyaevo-tartaric  acid,  k  =  0.097 

Dextro-tartaric  acid,  k  =  0.097 

Racemic  acid,  k  =-  0.097 

Inactive  non-racemic  acid,  k  =  0.060 

Fumaric  acid,  k  =  0.093 

Maleicacid,  k  =  1.17 
This  constant  k  is  in  direct  relation  with  the  coefficient  of  acidity  of  acids 

which  was  calculated  by  Thomsen.     This  leads  to  the  name  'affinity  constant' 

which  has  often  been  given. 


Bischoff  :  Ber.  d.  chem.  Ges.,  24,  1048  ;  Zelinsky :  Ibid.,  24,  3997. 


122  ELEMENTS   OF   STEREOCHEMISTRY 

CH2CH2COOH,  and  its  monoalkyl  derivatives,  CH3COCH. 
(CH3)CH2COOH,    which     form     anhydrids,    or,    more 
strictly  speaking,  unsaturated  lactones. 
=  C(CH3)—  CH2 


O  -  ----  CO 

The  alcoholic  radicals  exert,  without  doubt,  a  decided 
action  on  the  formation  of  cyclic  compounds.  According 
to  the  dynamic  hypothesis  of  Bischoff,1  these  facts  would 
be  in  relation  with  the  collision  of  atomic  groups  or 
radicals  in  the  interior  of  the  molecule. 

b.  Configuration   of   cyclic   compounds    of     carbon.  — 

The  properties  of  some  saturated  compounds  allow  the 
conception  of  relative  distance  between  the  groups  which 
compose  them,  and  of  defining  the  configuration  of  the 
molecule.  The  hydrocarbons  themselves  furnish  the 
most  simple  example.  The  structural  formula  of  a 
paraffin,  CH3i.CH22.CH23.CH24;CH25.—  CH3W,  does  not 
give  an  exact  idea  of  the  relative  distance  between  the 
groups,  for  Ci  appears  nearer  to  C2  than  to  €3.  But  if 
one  represent  hydrocarbons  such  as  butane  and  pentane 
by  solid  figures,  one  obtains  the  following  pictures  : 


Fig.  19. 
Ber.  d.  chem.  Ges.,  23,  265. 


GEOMETRICAL   ISOMERISM 


123 


Fig.  20. 

which  one  can  conceive  as  a  simple  phase  of  intra- 
molecular movement.  As  a  consequence  of  the  dimensions 
of  the  tetrahedra  which  are  assumed  in  this  case  to  be 
regular,  the  distance  of  the  first  tetrahedron  from  the 
four  others,  measured  from  the  center,  will  then  have  the 
relation 

i  :  i. 02  :  0.67  :  0.07. 

These  relations  represent  approximately  the  relative  dis- 
tances of  the  groups  united  to  the  carbon  atoms  at  the 
moment  of  maximum  approach.  In  conformity  with 
this  it  follows  that  the  majority  of  intramolecular 
reactions  which  take  place  in  saturated  compounds  are 
effected  with  greater  difficulty  between  neighboring 
groups,  that  is  to  say  in  the  ^-position,  with  more  diffi- 
culty than  between  the  groups  i  and  3  or  ft- position,  but 
very  easily,  much  more  frequently,  and  even  spon- 
taneously between  the  groups  i  and  4  and  i  and  5,  or  in 


124  ELEMENTS   OF   STEREOCHEMISTRY 

the  y~  and  (^-positions.    Thus  it  is,  that  the  chlorhydrins1 
lead  to  the  ethylene  oxids, 

OH 

=CI(H2»0 


while  the  oxy-acids  give  lactones, 


Cn  H  =  Cn  H  +  H20 

\COOH  ^CO/ 

which  are  formed  exceedingly  easily  by  starting  from  the 
y-  and  ^-derivatives,  and  exceptionally  by  using  the  fi- 
derivatives,  but  never  in  the  case  of  ^-derivatives.2 
Starting  from  the  derivatives  such  as  the  lactic  acid  two 
molecules  enter  into  the  reaction  and  thus  form  a  chain 
consisting  of  these  atoms  ;  e.g.,  the  lactid, 

CH3.CH—  CO—  O 

!  I 

O  —  CO—  CH.CH3 

The  a-  and  y^-amido  acids  are  not  decomposed  in  the 
same  way  as  the  y-  and  tf-amido  acids  into  water  and 
lactams  (pyrrolidones  and  piperidones)  ;  one  does  not 
know  of  an  anhydrid  of  oxalic  and  malonic  acids,  but 
succinic  and  glutaric  acids  whose  carboxyl  groups  are  in 
the  y-  and  (^-position  to  one  another  yield  anhydrids 
without  difficulty. 

/COOH  /COV 

Cn  H    /  =  Cn  H    /  0  +  H20  . 


It  should  be  noticed  that  changes  of  constitution  may 
modify  the   preceding  reactions  ;  for  example,  the  pres- 

1  Kvans  :  Ztschr.  phys.  Chem.,  7,  337. 

2  Wislicenus:  "  Anordung  der  Atome,"  p.  67. 


GEOMETRICAL   ISOMERISM  125 

ence  of  certain  groups,  such  as  alcohol  radicals  favor  the 
transformation  of  dibasic  acids  into  anhydrids  and  of 
oxy-acids  into  lactones.  In  the  same  way  the  formation 
of  the  lactocarboxylic  acid  derivatives  of  the  dicarboxy- 
oxy-acids  appear  to  be  facilitated  by  the  presence  of  the 
two  carboxyl  groups.  This  is  also  in  agreement  with 
the  results  obtained  from  the  investigation  of  the  molec- 
ular conductivity  of  these  acids.  Wislicenus  has 
explained  in  the  same  way  the  characteristic  decom- 
position which  the  /^-halogen  acids  undergo  when  treated 
with  sodium  carbonate, 

COONa.CH2CHBrR  ==  CO2  +  NaBr  +  CH2:CHBr. 

The  ^-halogen  acids  are,  on  the  other  hand,  much  more 
stable,  as  the  sodium  atom  of  the  group  COONa  is 
nearer  to  the  halogen  atom  in  the  first  case  than  in  the 
second.  This  will  be  easily  seen  by  using  solid  models. 
There  only  remains  to  be  mentioned  the  transformation 
of  y-diketones  and  compounds  of  this  kind  into  cyclic 
derivatives  of  furfufan,  pyrrol,  and  thiophen. 

CH2.CO.R          CH—CR 
|  =      |  >  (O.NH.S)  +  H20. 

CH2  CO  R          CH—CR 

III.  STEREOCHEMISTRY  OF  CYCLIC  COMPOUNDS. 

a.  General. — The  tetrahedral  theory  is  the  basis  of  the 
new  and  very  striking  development  which  concerns  the 
formation  and  configuration  of  cyclic  compounds.  It 
suffices  to  allow  that  the  four  valences  of  a  carbon  atom 
considered  as  isolated  forces  acting  normally  in  the  direc- 
tion of  the  four  summits  of  a  regular  tetrahedron,  can  be 
diverted  from  their  original  direction.  Thus  this  diver- 
sion will  naturally  produce  an  increasing  tension  in  the 


126  ELEMENTS   OF   STEREOCHEMISTRY 

interior  of  the  molecule.1  (Baeyer's  tension  theory.) 
This  idea  takes  into  account  the  properties  of  ethylene 
derivatives  which  are  regarded  as  compounds  of  dimethyl- 
ene,  but  it  is  principally  of  use  in  the  study  of  poly- 
methylene  compounds. 

The    configuration    of    polymethylene    derivatives. — 

One  must  admit,  in  compounds  characterized  by  double 
or  triple  linkages,  that  the  valences  act  as  forces  par- 
allel to  one  another  ;  in  consequence  they  act  as  a  re- 
sult of  being  deviated  from  their  original  direction,  and 
this  also  holds  good  with  cyclic  compounds.  The  size  of 
the  deviation  angle  serves  to  measure  approximately  the 
forces  or  tension  which  tend  to  the  return  of  the  valence 
to  its  normal  position.  One  can  conceive,  therefore,  that 
these  forces  and  consequently  the  angle  on  which  it 
depends,  are  in  inverse  ratio  to  the  stability  of  closed 
chains.  In  the  tetrahedral  scheme  which  represents 
methane,  two  of  the  valences  form  an  angle  of  109°  28'. 
In  supposing  the  centers  of  the  different  atoms  of 
carbon  to  be  situated  in  the  same  plane,  this  angle  would 
have  the  following  values  in  polymethylene  compounds. 


CH2                        CH, 

CH2—  CH2 

II                         /\ 

1           1 

CH2              H2C  CH2 

CH—  CH2 

Dimethylene              Trimethylene 

Tetramethvlene 

+  54°  44'.                   +  24°  44'. 

9°  34'-  ' 

CH2 

CH2—  CH2 

/\                      HC 

/'         VH 

CH2     CH2                ^^ 

\          /CH2 

\            \ 

CH2—  CH2 

CH2—  CH2 

Pentamethylene 

Hexamethylene 

+  o°44'.!  -5°  16'. 

Baeyer :  Ber.  d.  chem.  Ges.,  18,  2279. 


GEOMETRICAL   ISOMERISM  127 

The  deviation  is  then  at  its  maximum  in  the  ethylene 
compounds  ;  this  corresponds  to  the  maximum  of  tension, 
and  explains  why  these  chains  are  easily  broken,  for,  as 
is  well  known,  the  mere  presence  of  iodin  is  sufficient  to 
produce  this  change.  The  trimethylene  ring  is  more 
stable,  although  it  also  breaks  when  treated  with  hydro- 
bromic  acid  ;  finally  closed  chains  with  four  and  five 
atoms  of  carbon  are  only  broken  with  difficulty  in  reac- 
tions involving  addition.  These  characteristics  are  shown 
in  the  figures  on  pages  122  and  123.  The  closed  chain  with 
two  carbon  atoms  is  the  form  obtained  with  the  greater 
expenditure  of  energy,  than  a  chain  containing  five  carbon 
atoms.  The  calorimetric  results  of  Stohmann1  confirm 
this  view,  as  the  heat  consumed  in  forming  a  chain  con- 
taining two  or  three  carbon  atoms  is  practically  the  same 
as  that  used  in  a  tetramethylene  synthesis,  while  the 
formation  of  penta-  and  hexamethylene  compounds, 
consumes  a  quantity  of  heat  which  is  much  smaller. 

The  configuration  of  the  polymethylene  compound  is 
not  without  its  analogy  to  that  of  ethylene.  All  the 
atoms  of  carbon  are  in  the  same  plane,  which  one  may 
term  as  the  annular  plane,  and  the  atoms  of  hydrogen 
united  to  the  carbon  are  in  two  parallel  planes,  situated 
on  each  side  of  the  primitive  plane.  The  tension  theory 
applied  to  the  tri,  tetra,  and  penta  derivatives  of 
methylene  is  in  favor  of  this  view,  for  it  is  under  these 
conditions  that  one  gets  the  minimum  tension  of  the 
valences  of  carbon.  One  can  bring  experimental  facts  as 
proof  also  ;  for  example,  one  obtains  cases  of  isomerism 
analogous  to  those  which  have  been  found  in  the 
ethylene  series  and  which  may  be  mentioned  further  on. 
But  in  the  case  of  hexamethylene  compounds  the  con- 

1  Stohmann  :  J.  prakt.  Chem.,  45,  475. 


128  ELEMENTS   OF   STEREOCHEMISTRY 

ditions  are  such  as  to  require  special  consideration. 
Here,  regular  tetrahedra  have  been  united  to  one  another 
by  their  summits  to  form  a  closed  chain  without  com- 
pelling one  to  assume  a  deviation  of  the  valences  from 
their  original  direction.  This  may  be  done  in  two  ways. 
Suppose  that  the  carbon  atoms  are  not  all  in  the  same 
plane  ;  then  one  may  get  first,  an  immovable  symmetrical 
configuration  with  a  regular  distribution  of  the  two  atoms 
of  carbon  in  two  parallel  planes,  and  an  orientation  of 
the  twelve  atoms  of  hydrogen  in  three  parallel  planes, 
and  second,  a  mobile  unsymmetrical  constitution  without 
any  fixed  position  for  the  atoms  of  carbon  and  hydrogen. 
According  to  this  hypothesis  which  is  due  to  Sachse,  the 
symmetrical  configuration  would  indicate  two  mono- 
substituted  stereoisomers,  and  as  a  matter  of  fact,  two 
hexahydrobenzoic  acids  are  known,  one  obtained  by  the 
reduction  of  benzoic  acid,  the  other  being  the  hexa- 
naphthalenecarboxylic  acid. 

Configuration  of  the  Cyclic  Compounds,  (CH)n 

Benzene  derivatives. — In  acetylene,  HC  =  CH,  three  of 
the  valences  of  carbon  are  deviated  70°  32'  which  corre- 
spond to  strong  tension  and  consequently  unstability. 
One  can  consider  the  acetylene  molecule  as  plane  ;  that  is 
to  say,  that  the  atoms  of  carbon  and  hydrogen  of  which 
it  is  composed  are  situated  in  the  same  plane.  It  is 
•  probable  that  other  bodies  of  this  kind  (benzene,  naph- 
thalene, phenanthrene)  have  an  analogous  configuration, 
or  in  other  words,  in  these  compounds  the  carbon  atoms 
are  arranged  in  an  annular  plane.  One  can  only  bring 
certain  negative  proofs  to  bear  on  this  view,  particularly 
the  fact  that  up  to  the  present,  one  has  not  found  stereo- 
isomers among  the  substitution  derivatives  of  these 


GEOMETRIC AI<   ISOMERISM  129 

hydrocarbons,  and  that  all  the  efforts  made  in  the  direc- 
tion of  separating  them  into  two  components  have 
remained  fruitless.1 

Among  the  views  brought  forward  in  this  connection 
the  work  of  Wunderlich2  should  be  mentioned,  who 
asserted  that  atoms  had  a  definite  solid  form  (the  tetra- 
hedral  form  for  carbon),  of  Werner  on  affinity  and 
valence,  and  of  Hermann,  who  dispenses  with  all  hypo- 
theses regarding  the  nature  of  the  carbon  atoms  and  who 
uses  strictly  geometrical  figures. 

Lastly  Friedel3  observes  that  if  one  considers  the 
Kekule  formula  in  the  light  of  his  tetrahedral  scheme, 
the  only  objection  which  has  been  made  against  this 
formula  disappears.  This  objection  was  raised  in  con- 
sidering the  possibility  of  two  ortho  derivatives  of  ben- 
zene. With  a  very  small  normal  tension  of  the  valences 
(3°,  46')  one  may  construct  a  hexagonal  scheme  in 
which  the  distances  of  the  atoms  of  hydrogen  in  benzene 
are  equal ;  consequently  the  reciprocal  action  between 
these  atoms  will  also  be  equal  and  the  possibility  of  the 
existence  of  two  ortho  derivatives  is  dispensed  with. 

b.  The  geometrical  isomerism  of  the  polymethylene 
derivatives. — Geometrical  isomerism  exists  in  the  poly- 
methylene derivatives  as  it  does  in  those  of  ethylene,  for 
the  formation  of  a  cyclic  compound  arrests  the  mobility 
of  the  atoms  of  carbon  as  it  does  the  double  bond.  It 
has  been  seen  in  the  geometrical  isomers  of  ethylene, 
that  they  are  represented  by  schemes  in  which  the  atoms 
are  oriented  differently  in  relation  to  the  plane  of  the 
double  bond.  In  the  same  way  the  stereoisomeric  poly- 

1  lye  Bel :  Bull.  Soc.  Chim.,  38,  398;  I^ewkowitsch :  Ber.  d.  chem.  Ges.,  16, 
1578. 

2  "Organische  Molekiile,"  1886. 

3  Friedel  :  Bull.  Soc.  Chim.  (3),  5,  130. 

9 


130 


ELEMENTS   OF   STEREOCHEMISTRY 


rnethylene  compound  will  be  represented  by  figures  in 
which  the  atoms  are  placed  differently  with  respect  to  the 
annular  plane.  These  compounds,  therefore,  give  two 
stereoisomeric  disubstitution  products  according  as  the 
two  atoms  of  hydrogen  are  both  on  the  same  side  of  the 
plane,  or  are  separated  by  it.  The  most  important  poly- 
methylene  stereoisomers  belong  to  the  hexamethylene 
series.  Among  the  hydrocarbons  of  this  series  may  be 
mentioned  the  two  dihydroterpenes  (methylisopropyl- 
hexamethylenes)  ;  among  the  halogen  derivatives  two 
hexachlorids  of  benzene,  C6H6C16  ;l  among  the  hydroxyl 
compounds  two  paradioxyhexamethylenes,  C6H10(OH)2 
(quinites),  obtained  synthetically;2  then  several  hexoxy- 
hexamethylenes ;  viz.,  two  iuosites,  C6H6(OH)6,3  two 
pinites,  C6H6(OH)5.OCH3,  and  lastly  numerous  stereo- 
isomeric polymethylene  acids.  These  acids  are  compar- 
able to  f umaric  and  maleic  acids,  from  which  one  gets  the 
following  scheme : 


H 


H 


H 

I 


H      (CH2)W 


(CH2)«(_ 


COOH     COOH 

Maleic  acid. 

COOH     H 

I  I 

C      = 


COOH  COOH 

Maleic  acid  or  cis  form. 


H 


C 

I 

COOH 
Fumaric  acid. 


(CH,)' 


H 

I 


COOH 


\_C C 

COOH  H 

Fumaroid  or  cistrans  form. 


1  Friedel:  Bull.  Soc.  Chim.  (3),  5,  130. 

2  V.  Baeyer :  Ber.  d.  chem.  Ges.,  25,  1037  and  1804. 

3  Maquenne :  Ann.  china,  phys.  (6),  22,  264. 


GEOMETRICAL   ISOMERISM  131 

Experimentally  there  have  been  found  several  acids  cor- 
responding to  the  maleinoid  type.  These  are  character- 
ized by  their  solubility,  their  low  melting-points  and 
their  pronounced  acid  reaction,  and,  on  the  other  hand, 
other  acids,  less  soluble  and  melting  less  readily  which 
correspond  to  fumaric  acid.  These  latter  are  formed  by 
direct  molecular  transposition,  by  means  of  hydrochloric 
acid,  which  indicates  their  relative  stability,  while  the 
less  stable  modifications  can  be  looked  upon  as  the  direct 
product  of  the  reduction  of  polymethylene  acids.  These 
properties  are  met  with  in  the  dicarboxyl,  and  tricarboxyl 
derivatives  of  trimethylene,  which  are  found  in  two 
modifications  j1  in  the  numerous  hexamethylene  dicar- 
boxylic  acids,  and  in  particular  in  the  hexahydrogen 
derivatives  of  phthalic'2  and  terephthalic3  acids,  and  in  the 
hexahydromellitic4  acids.  These  acids  are  distinguished 
somewhat  from  fumaric  and  maleic  acids  in  the  way  in 
which  they  give  an  anhydrid,  which  forces  one  to 
assume  relative  remoteness  of  the  two  carboxyl  groups. 
The  cisdicarboxylic  acids  in  which  the  two  carboxyl 
groups  are  close  together,  e.  g.,  the  cishexahydrophthalic 
acid  are  transformed  easily  into  anhydrids  corresponding 
in  this  particular  to  maleic  acid  ;  but  the  cisdicarboxylic 
acid  in  which  the  carboxyl  groups  are  separated  by 
several  atoms  of  carbon  does  not  do  so.  For  example,  the 
hexahydroterephthalic  acid  does  not  give  an  anhydrid. 

1  Buchner  :  Ber.  d.  chem.  Ges.,  27,  702;  Conrad  "and  Gutzheit :  Ibid.,  17, 
1186. 

-  v.  Baeyer  :  Ann.  Chem.  (I^iebig),  258,  145. 

3  v.  Baeyer:  Ibid.,  245,   103;   251,   257  ;  256,  i  ;   258,  i  and  145  ;   266,  169; 
269,  145 

4  v.  Baeyer  :  Ber.  d.  chem.  Ges.,  i,  118. 


132  ELEMENTS   OF   STEREOCHEMISTRY 


H' 

Cishexabydrophthalic  acid,  yielding  an  anhydrid. 

H  H 

'h 
H 


.COOH 


H  H 

Cishexahydrophthalic  acid,  not  yielding  an  anhydrid. 

Conversely  and  worthy  of  note  is  the  fact  that  certain 
transdicarboxylic  acids  of  the  fumaroid  type  give  anhy- 
drids  which  are  different  from  those  yielded  by  the  cis 
acids,  and  can  be  transformed  into  the  latter.  Thus,  the 
formation  of  anh)rdrids  is  only  possible  when  the  two 
carboxyl  groups  are  united  to  neighboring  carbon  atoms, 
and  depends  besides  on  other  conditions.  Thus,  starting 
with  the  two  hexahydrophthalic  acids,  cis  and  trans, 

H 

~\  ^  "\ 

>H2 

COOH     H  /: 

I / 

COOH  H  COOH 

Cistrans. 

one  may  prepare  two  stereoisomeric  anhydrids  while  with 
the  trimethylene  dicarboxylic   acids, 


GEOMETRICAL   ISOMERISM 


133 


H 

A 


COOH 


COOH 


H 


Cis. 


Cistrans. 


the  trans  modification  does  not  give  anhydrids  any  more 
easily  than  fumaric  acid  itself.  One  may  explain  these 
facts  in  the  following  way.  The  valences  united  to  the 
carboxyl  groups  form  between  them  an  angle  of  180° 
which  may  be  shown  readily  on  the  solid  model,  while  in 

COOH 


COOH 


Fig.  21. 


the  f  umaroid  hexahydrophthalic  acid  the  replacing  of  the 
double  bond  (e.g.,  the  chain  C2)  by  the  ring  C6  reduces 
this  angle  to  something  less  than  109°  ;  this  angle  then 
becomes  nearly  equal  to  the  angle  of  the  valence  in  the 
original  tetrahedron.  With  the  corresponding  acids  of 
tri-,  tetra-,  and  pentamethylenes  the  angle  is  intermediate 
between  the  two  extreme  values  of  1 80°  and  109°.  As  a 
result,  in  cyclic  compounds,  as  the  number  of  carbon  atoms 
increases  the  angle  in  question  diminishes,  and  con- 
sequently the  distance  between  the  two  carboxyl  groups. 
This  explains  why  the  transdimethylene  dicarboxylic 
acid  and  the  transtrimethylene  dicarboxylic  acid  do 
not  give  anhydrids,  while  one  has  been  able  to  isolate  an 
anhydrid  of  the  transhexahydrophthalic  acid. 


134  ELEMENTS   OF   STEREOCHEMISTRY 

The  optical  and  geometrical  isomerism  of  polymethylene 
compounds.  —  The  geometric  isomers  of  ethylene  without 
a  symmetric  carbon  atom  do  not  present  molecular  dis- 
symmetry ;  but  this  dissymmetry  may  be  met  with  in  the 
geometrical  isomers  of  polymethylene  acids.  The  pres- 
ence of  two  asymmetric  carbon  atoms  renders  them 
analogous  to  the  derivatives  of  tartaric  acid,  or  more 
closely  to  the  dialkyl  succinic  acids.  The  structural 
analogy  which  exists  for  instance  between  dimethyl 
succinic  acid  and  hexahydrophthalic  acid  is  shown  in  the 
following  formula  : 


CH3  ,  CH—  CH2 

^CHCOOH—  CHCOOH     CH2  CH2 

Dimethyl  .succinic  acid.          \  / 

CHCOOH—  CHCOOH 

Hexahydrophthalic  acid. 

The  hexahydrogenated  cis  acid  is  thus,  from  a  stereo- 
chemical  point  of  view,  comparable  to  non-racemic  inactive 
dimethyl  succinic  acid  (corresponding  to  inactive  tartaric 
acid). 


CH 


COOH—  C—  H  COOH—  C—  H        CH2 

I  I  I 

COOH—  C—  H  COOH—  C—  H         CH2 

CH3  X 

CH2 

The  trans  acid,  on  the  other  hand,  maybe  compared  to 
racemic  dimethyl  succinic  acid  (corresponding  to  racemic 
acid,  although  it  has  not  yet  been  decomposed  into  its 


GEOMETRICAL   ISOMERISM 


135 


two  isomers).     It  should  thus  exist  in  two  enantiomor- 
phous  modifications  : 


CH 


CH3 

COOH— C— H  COOH— C— H 

H— C— COOH 
CH3 


H— C— COOH      CH2 


CH, 


Cis  acids  or  those  corresponding  to  the  maleinoid  type 
are  hence  inactive  by  intramolecular  compensation.  The 
trans  or  fumaroid  acids,  on  the  contrary,  are  rendered 
inactive  by  intramolecular  compensation.  The  first  are 
incapable  of  decomposition  in  a  stereochemical  sense  ; 
the  latter  should  be,  although  experimentally  this  has 
not  yet  been  realized.  The  existence  of  a  laevo-  and 
dextroinosite,  CH(OH)6,  shows  besides,  that  optical 
inactivity  can  exist  in  cyclic  compounds  and  especially  in 
substances  containing  the  hydroxyl  group. 


136  ELEMENTS   OF   STEREOCHEMISTRY 

c.  The  geometrical  isomerism  of  cyclic  compounds 
with  double  bonds. — The  isomerism  here  is  of  the  same 
kind  as  that  which  has  already  been  described  and  has 
only  been  observed  in  that  group  of  compounds  which 
are  the  result  of  the  plane  reduction  of  benzene  and 
naphthalene.  Among  these  the  many  compounds 
belonging  to  the  di-  and  tetrahydrogen  derivatives  of  the 
dicarboxylic  acids  of  benzene  are  the  result  of  the  work 
of  v.  Baeyer  ;  they  form  stereoisomers  analogous  to  those 
of  the  hexahydrogen  acids  ;  thus  one  has  : 


COOHx     'H== — H\    sCOOH 

> 


H/    X H/'\H 

Cis  non-racemic. 


COOH^/H.      Jx/H 

H/\-  -H/\COOH 

Cis  trans  racemic. 

Theracemic  dihydrophthalic  acid,  which  has  been  split 
up  into  two  isomers  by  Proost,1  furnishes  an  example  of 
substances  belonging  to  this  class. 

The  trans  dihydrophthalic  and  tetrahydrophthalic 
acids  also  give  anhydrids  which  may  be  transformed 
into  anhydrids  of  cis  acids.  The  atomic  arrangements 
which  characterize  mixed  cyclic  compounds  have  not  yet 
been  fixed ;  it  is  therefore  probable  that  conversely  to 
that  which  has  been  observed  in  the  polymethylene  com- 
pounds, and  in  the  derivatives  of  the  type  (CH)W,  the 
atoms  of  carbon  in  the  benzene  nucleus  are  not  in  the 

1  Proost:  Ber.  d.  chem.  Ges.,  27,  3185. 


GEOMETRICAL   ISOMERISM  137 

same  plane  ;  hence,  one  would  not  here  have  to  deal  with 
an  annular  plane.  As  a  result  of  this,  the  stereoisomerism 
of  these  compounds  would  become  still  more  complex, 
and  the  terpene  series,  and  the  group  of  derivatives  of 
camphor  furnish  an  example  of  this  statement. 

d.  The  geometrical  isomerism  of  compounds  analo- 
gous to  polymethylene  derivatives. — Among  the  satura- 
ted cyclic  compounds,  the  piperazones1  with  two  asym- 
metric carbon  atoms  of  the  formula, 

C'H(R)—  CO 

/  \ 

C6H5— N  N— C6H5, 

CO— CH(R) 

exist  in  two  isomeric  modifications,  corresponding  to  the 
dialkyl  succinic  acids  ;  the  trithioaldehydes,   (RCHS)3, 
regarded  as  derivatives  of  trithiomethylene,2 
S— CHR 

/  \ 

CHR  S,  also  give  two  isomers  corresponding  to  the 

S CHR 

configurations, 

R  R 


/H\  /H 

R/S  \     R        H      /S  S\H 

\-^-  -s ^-H         f-^C   _s-    :^H, 

H  H         R  R 

These  configurations  are  borne  out  by  the  fact  that  the 
unstable  cis  derivatives  when  heated  slightly  above  their 

1  Bischoff :  Ber.  d.  chem.  Ges.,  25,  2999. 

2  Baumann  :  Ibid.,  24,  1425. 


J38 


OF   STEREOCHEMISTRY 


melting-point  give,  by  partial  oxidation,  a  disulfone 
sulfid  ;  on  the  other  hand  the  stable  and  higher  melt- 
ing trans  derivatives  give  two  stereoisomeric  sulfids  of 
disulfone. 

R 

/k 
/H\ 


so, 


R      / 

1      / 

1 
H 
R 

/k 
/H\ 

[     /S0>         S\ 
'             S 

H 

^     1 

I 

1 
R 

SO2 


N 


R 


H 
R 


R 


One  may  explain  in  the  same  manner  the  isomerism  of 
metaldehyde  and  paraldehyde  which  may  be  represented 
by  the  figures 

CH3  CH3 

/l\ 

/H\ 
O  O  O 


o 

^— 0- 


\ 


CH3CH3/ 


H 


H 


Cis  paraldehyde  (?)  . 


H 


H       H 
H 

/H\ 
O 

-O— ^ 


CH3 

Cistrans  metaldehyde  (?). 


H 


H 

Paraformaldehyde. 
1  Friedel:  Bull.  Soc.  Chim.  (3),  9,  384. 


H 


GEOMETRICAL   ISOMERISM  139 

In  agreement  with  this  explanation  one  has  the  experi- 
mental evidence  that  formic  aldehyde  gives  but  one 
polymer. 

IV.  THE  GEOMETRICAL  ISOMERISM  OF  NITROGEN 
Theoretical. — It  has  been  seen  in  the  foregoing  that 
the  absence  of  optical  isomers  among  the  ammonium 
bases  of  the  type  NRR'R"  tends  to  prove  that  the  three 
valences  of  nitrogen  are  situated  in  the  same  plane. 
However  this  element  does  not  always  behave  in  this 
way,  even  when  it  acts  in  a  trivalent  sense  ;  consequently 
it  can  give  rise  to  cases  of  isomerism  which  correspond 
very  closely  with  the  geometrical  isomerism  of  ethylene 
compounds.1 

The  following  are  some  considerations  on  which  is 
based  the  conception  of  geometrical  isomerism  in  nitrogen 
compounds.  In  assuming  that  the  trivalent  nitrogen 
N'"  is  equivalent  to  the  group  (CH)'",  one  can  replace 
in  any  derivatives  containing  (CH)  one  or  more  of  these 
groups  by  nitrogen  atoms.  Thus,  hydrocyanic  acid, 
HC=N,  corresponds  to  acetylene,  CH=CH,  pyridin, 
(CH)5N,  and  the  diazins,  (C6H)4N2,  to  benzene,  (CH)6, 
and  as  three  valences  of  carbon  directed  towards  the 
summit  of  a  tetrahedron  can  be  replaced  by  nitrogen,  it 
is  necessary  to  conclude  that  in  these  bodies  the  three 
valences  of  nitrogen  are  also  directed  towards  the  angles 
of  a  tetrahedron  (which  cannot  be  a  regular  one),  of 
which  the  nitrogen  atom  occupies  the  fourth  summit. 

Hence,  compounds  analogous  to  acetylene,  i.e.,  the 
nitriles,  do  not  present  the  phenomena  of  isomerism.  On 
the  other  hand,  just  as  the  ethylene  derivatives  give  two 
isomers,  the  compounds  with  a  double  linkage  between 
an  atom  of  carbon  and  an  atom  of  nitrogen,  and  the  com- 

1  Hantzsch  and  Werner  :  Ber.  d.  chem.  Ges.,  23,  i  and  1243. 


140  ELEMENTS   OF   STEREOCHEMISTRY 

pounds  with  a  double   linkage   between   two   atoms  of 
nitrogen  will  occur  in  two  modifications. 

Experimentally  these  different  cases  of  isomerism  have 
been  observed,  and  it  will  be  necessary  to  make  a  similar 
classification  to  that  which  was  followed  out  in  the  study 
of  geometric  isomers  of  the  preceding  compounds. 

1 .  Derivatives  of  geometrical   isomeric   carbon   of  the 
general  formula,  abC  :  CW,    corresponding  to   two   con- 
figurations, 

a— C— b  a—C—b 

II  II        • 

^—  C— d  d—C-c 

2.  Geometrical  isomers   of  carbon  and  nitrogen  of  the 
general  formula,  adC  :  NV,  corresponding  to  the  two  con- 
figurations, 

a— C— b  a—C—b 

II  II        , 

c—  N  N— c 

of  which  the  best  known  examples  are  the  oximes,  the 
hydrazones,  and  the  imido  compounds. 

3.  Derivatives  of  double  linked  nitrogen  of  the  general 
formula,  0N  :  NV,  corresponding  to  the  two  configurations, 

a— N  a— N 

II  II        , 

c— N  N— c 

of  which  the   most   important   representatives  are  found 
among  the  diazo  and  azo  compounds. 

It  is  still  possible  that  compounds  containing  a  single 
linkage,  nitrogen  (for  example,  the  derivatives  of 
hydrazin,  ab'N.Ncd),  exist  in  two  modifications,  indicated 
by  the  following  : 


GEOMETRICAL   ISOMERISM  141 

a— N—  b  a—^—b 

I  I 

c—  N— d  d—^—c 

The  two  modifications  of  picrylhydrazin,1  C6H5NH. 
NHC6H2(NO2)3,  correspond  perhaps  to  these  two  modi- 
fications. 

The  general  properties  of  the  geometric  isomers  of  ni- 
trogen.— The  characteristics  which  differentiate  the  geo- 
metric isomers  of  nitrogen  are  comparable  to  those  dis- 
tinguishing the  carbon  compounds.  They  are  met  with 
in  all  the  physical  and  chemical  properties  which 
depend  on  intramolecular  reactions,  and  the  distance 
between  the  atoms.  Spatial  formulae  explain  the 
chemical  characteristics  of  the  nitrogen  isomers,  as  well 
as  those  of  the  corresponding  ethylene  compounds. 
According  to  this  view,  it  is  necessary  to  assume  that  the 
geometric  isomers  of  nitrogen  have  the  characteristic 
property  of  passing  very  easily  from  one  configuration  to 
another,  and  similarly  the  affinity  constants  are  different 
for  compounds,  such  as 

R— C— COOH  R— C— COOH 

II  II 

HO— N  N— OH 

Geometric  isomeric  oximido  carboxylic  acids. 

as  for 

R— C— COOH  R— C— COOH 

II  II 
COOH    C— H                      H   C— COOH 

Geometric  isomeric  ethylene  carboxylic  acids. 

In  both  cases  the  constants  vary  between  the  same 
limits.  These  facts  are  explained  clearly  if  one  assumes, 

1  Willgerodt :  J.  prakt.  Chem.,  41,  297. 


142  ELEMENTS   OF   STEREOCHEMISTRY 

as  with  the  ethylene  derivatives,  that  the  nitrogen  com- 
pounds are  true  stereoisomers.1 

The  explanation  of  the  geometrical  isomerism  of 
nitrogen  compounds  has  been  sought  for  as  was  formerly 
done  in  the  case  of  the  ethylene  compounds  by  using 
constitutional  formulae.  The  following  explanation  gives 
the  reasons  why  this  interpretation  has  been  abandoned. 
In  the  first  place,  the  number  of  known  isomers  does  not 
coincide  with  the  number  of  the  different  constitutional 
formulae,  which  can  be  conceived  for  these  compounds; 
besides,  one  cannot  explain  why  compounds  of  the 
symmetric  structure  aaC  :  N<^-give  but  one  modification, 
while  those  of  asymmetric  structure  give  two.  Hence, 
one  would  be  forced  to  represent  these  two  types  by 
different  structural  formulae,  which  would  be  to  a 
greater  or  less  extent  problematical,  for  one  knows  that 
the  oximes  of  the  aromatic  series  and  of  the  aliphatic 
series  do  not  behave  in  the  same  way.  In  this  case,  the 
mutual  transformation  of  these  isomers  would  be  no 
longer  attributable  to  the  same  causes.  Lastly, 
structural  formulae  would  not  explain  intramolecular 
transpositions,  nor  the  evident  analogy  of  isomers  derived 
from  nitrogen  with  those  of  the  stereoisomeric  ethylene 
derivatives. 

V.  THE   GEOMETRICAL  ISOMERS  OF  CARBON  AND 
NITROGEN 

a.   The   historical  proofs  of   identical  constitution. — 

The     two    benzildioximes     corresponding    to    formula 

C6H5NOH.CNOH.C6H5 
were  first   isolated  by   Goldschmidt,2   and  v.  Meyer  and 

1  Hantzsch  and  Miolati  :  Ztschr.  phys.  Chem.,  10,  i. 

2  Ber.  d.  chem.  Ges.,  16,  2176. 


GEOMETRICAL   ISOMERISM  143 

Auwers1  proved  that  these  two  compounds  had  the  same 
constant,  and  discovered  a  third  isomer  ;2  they  thought 
to  explain  the  cause  of  this  isomerism  by  assuming  that 
the  simple  bond  between  the  two  atoms  of  carbon  had 
ceased  to  be  completely  mobile. 

C6H6—  C=NO.  H  C6H5— C= NOH 

C6H5— C— NOH  NOH^C— C6H5 

Beckmann,3  a  short  time  after  this,  prepared  an  isomer 
of  ordinary  benzaldoxime,  C6H5CH  :  NOH.  He  also 
considered  it  as  a  structural  isomer,4  and  gave  to  it  the 

C6H5.CH— NH 
formula  \  /         ,  although    Goldschmidt5    had 

O 

proved  the  structural  identity  of  the  two  benzaldoximes. 
These  facts  which  do  not  coincide  with  the  interpretation 
of  the  benzildioximes  which  had  been  given  by  v.  Meyer 
and  Auwers  induced  Hantzsch  and  Werner  to  the 
explanation  which  is  given  in  this  book,  and  which  led 
to  the  discovery  of  different  stereoisomeric  aldoximes, 
ketoximes,  dioximes,  oximido  acids,  etc.  At  first  these 
facts  appeared  difficult  of  explanation,  for  about  the  same 
time  it  was  proved  that  the  oximes  gave  rise  to  tautomeric 
phenomena.  The  group  (CNOH)  could  in  reality  react 
not  only  as  a  normal  group,  CNOH,  but  also  as  an  iso 

group, 

C  — NH 

\/       • 
O 

Now  the  general  formula  of  oximes, 

1  Ber.  d.  chem.  Ges.,  21,  784  and  3510. 

2  Ibid.,  22,  705. 

3  Ibid.,  20,  2766  ;  Ibid.,  22,  432. 

4  Ibid.,  22,  429,  514,  1531,  1588. 

5  Ibid.,  22,  3113. 


144  ELEMENTS   OF  STEREOCHEMISTRY 

Nc=NOR, 

b 

is  confirmed  by  reactions  which  they  undergo  without 
difficulty,  and  which  are  completed  under  conditions 
which  exclude  the  intervention  of  the  least  traces  of 
moisture.  One  thus  obtains  in  all  cases,  derivatives  of 
the  formula 


>C= NOR, 
and  not  of  the  formula 

\C N— R, 


Isomerism  in  oximes  is  also  found  among  other  sub- 
stituted products  ;  two  isomeric  compounds  corresponding 
to  the  formula 

a\ 
>C= N— OR 

K 

are  known.  These  two  bodies,  like  the  oximes  them- 
selves, are  mutually  transformed  one  into  the  other  in  a 
similar  manner  to  the  geometric  isomers  of  ethylene. 
Thus,  for  example,  two  isomers  of  each  of  the  alkyl  and 
acetyl  esters  are  known  : 

H\  R'\ 

>C= N— OCOCH3  >C= N.OCOCH3 

R/  R»/ 

The  same  is  true  with  the  alkyl  and  acetyl  esters  of  the 
hydroxamic  acids  : 


GEOMETRICAL   ISOMERISM  145 

ROV 

>C=N— 0(aHw+I) 
R/ 

ROV 

>C=NO(COCH3) 
R/ 

This  can  only  be  expressed  by  configuration  formulae  : 

(H).(R).(RO)—  C— R' 

II 
(CMH2W+1)(CH3COO)— N 

H.R.(RO)— C— R' 

II 
N-0(CH3CO)(CWH2W+1) 

Explanations  based  on  the  difference  in  the  structure  of 
the  group  (CNOH),  such  as  are  indicated  by  the 
formulae 

C N.H  /H 

No/  °r  C=N<Q 

must  thus  be  absolutely  abandoned. 

b.  The  different  classes  of  stereoisomeric  oximes.  De- 
termination of  their  configuration. 

Aldoximes  and  aldoximecarboxylic  acids. — Among  this 
class  of  compounds  one  defines  the  synaldoximes  in 
which  the  oximic  hydroxyl  and  the  aldehyde  hydrogen 
are  in  neighboring  positions,  and  the  antialdoximes  in 
which  the  two  groups  are  in  opposite  positions. 

R— C— H  R— C— H 

II  II 

N— OH  HO— N 

Synaldoxime.  Antialdoxime. 

The  synaldoximes  are  decomposed  as  the  formula 
would  indicate  into  water  and  nitriles.  This  reaction  is 

10 


146  ELEMENTS   OF   STEREOCHEMISTRY 

effected   more  or  less  easily,  according  to  the  nature  of 
the  radical  R.     It  is  produced  sometimes  with  the  oximes 
themselves,  as  in  trimethyl  benzaldoxime,  but  more  often 
with  their  acetates  or  their  phenyl  carbamic  esters, 
R— C— -H  R— C  H 

II  —  III      +     I 

N— (OH)X  N  OH(X) 

Under  the  same  conditions  the  antialdoximes  do  not 
undergo  any  change,  and  the  same  holds  good  for  their 
derivatives,  from  which  it  is  always  possible  to  reproduce 
unaltered,  the  original  oxime. 

This  kind  of  stereoisomerism  is  very  general  among  the 
aromatic  compounds.  It  is  found  in  the  oximes  of 
thiophene  and  of  furfuran.  Sometimes  however,  the 
differences  between  the  two  isomers  are  only  brought 
out  in  their  acetyl  derivatives.  This  is  the  case  with 
benzoyl  formoxime,  C6H5— CO— CNOH— H,  and 
aldoxime  acetic  acid  (/3-oximidopropionic  acid), 
COOH— CH2— CNOH— H.  The  aldoximes  properly 
speaking,  such  as  the  acetaldoxime  and  oenanthaldoxime, 
furnish  examples  of  this  class.  The  nature  of  the 
radical  R  exerts  a  great  influence  on  the  relative  stability 
of  the  two  configurations.  In  the  aliphatic  series  where 
R  =  C«Ha«  +  x  the  syualdoximes  are  more  stable,  but  in  the 
aromatic  series  the  antialdoximes  undergo  change  the 
less  readily.  Thus  one  will  have  : 

CWH2W  +  x — C — H  CWH2W  +  x     C    -H 

II  II 

N-OH  HO.N 

Stable  alkyl  synaldoxime.          Unstable  alkyl  antialdoxime. 

CHB— C— H  C6H5— C— H 

II  II 

NOH  HO— N 

Unstable  phenyl  synaldoxime .  Stable  phenyl  antialdoxime. 


GEOMETRICAL   ISOMERISM  147 

The  aldoxime  or  or-ketoxime  carboxylic  acids, 
R— CNOH— COOH,  resemble  the  aldoximes  in  their 
general  properties,  but  they  diffei  with  regard  to  their 
stability. 

Thus,  one   has   the  oximes  of  phenylglyoxylic   acid, 

C6H5— CNOH— COOH. 

C6H5— C— COOH  C6H5— C— COOH 

II  II 

N— OH  N— OH 

Stable  synphenylketoxime  Unstable  antiphenylketoxime 
carboxylic  acid.  carboxylic  acid. 

The  first  of  these  two  acids  which  contains  the  two 
groups  (OH)  and  (COOH)  in  neighboring  positions,  is 
the  only  one  which  gives  (as  in  the  synaldoximes)  an 
acetate  with  acetic  anhydrid. 

C6H5— C— COOH  C6H5— C— COOH 

II  —  II 

N— OH  N.O(CH3CO) 

C6H5— C  H 

HI     +     C02     +       |    (COCH3) 
N  O 

fi-Kctoximes. — The  structural  unsym metrical  ketox- 
imes  are  also  designated  by  the  prefixes  syn-  and  anti-; 
e.g.  : 

C6H-C-C6H4CH3       C6HB— C— C6H4.  CH3 

II  II 

HO— N  N— OH 

Synphenyltolylketoxime.  Atitiphenyltolylketoxime. 

These  configuration  formulae  allow  one  to  see  that  the 
differences  between  two  isomeric  ketoximes  should  be 
much  less  sharply  marked  than  those  of  the  aldoximes, 
for  the  two  groups,  R  and  R'  which  determine  the  dis- 
symmetry, have  much  more  in  common  than  the  H 


148  ELEMENTS   OF   STEREOCHEMISTRY 

and  R  of  aldehydes.  According  to  Hantzsch,  the  deter- 
mination of  the  configuration  is  based  on  the  trans- 
formation of  oximes  into  the  isomeric  amids 
(Beckmann's  reaction).  If  one  assume  that  the  inter- 
mediate products  vary  according  to  the  reagent  employed 
(H2SO4,HC1,PC15  and  H2O),  one  may  consider  this 
reaction  as  leading  to  a  change  of  position  between  the 
hydroxyl  united  to  nitrogen,  and  one  of  the  radicals 
united  to  carbon  in  the  molecule 

R/\ 

>C=NOH 

R"/ 

It  thus  forms  an  unstable  amido  modification,  for  example, 
HOV 

)C= NR' 
R"/ 

by  tautomeric  transposition  ;  and  this  passes  into  the 
stable  form,  the  true  amid 

0=C— NHR'. 
R"/ 

The  stereoisomeric  ketoximes  will  then  give  two  isomeric 
substituted  amids,  according  as  the  radical  R'  or  R" 
takes  the  place  of  the  hydroxyl.  But,  as  the  determina- 
tion of  the  configuration  by  the  study  of  intramolecular 
reactions  supposes  that  the  two  groups  which  entering 
into  the  reaction  occupy  neighboring  positions  (syn),  the 
radical  which  takes  the  place  of  the  hydroxyl  should  be 
in  a  contiguous  position  to  it. 

R'— C— R"      HO— C— R"  O  =  C— R" 

HO— N  R'N  HR'N 

R'— C— R"      R'— C— OH  R'— C  =  O 

11          —          11  I 

NOH  N— R"  N— R"H 


GEOMETRICAL   ISOMERISM  149 

Thus,  the  constitution  of  the  amid  which  has  been 
formed  allows  a  determination  of  the  configuration  of  the 
oxime  ;  for  the  radical  which  has  passed  from  carbon  to 
nitrogen  is  the  one  which  in  the  oxime  was  in  the 
vicinity  of  the  hydroxyl,  and  vice  versa.  Examples  : 

C6H5-C-C6H4.  (OCH3)  0=C-C6H4OCH3 

II  —  I 

HO—  N  C6H5.HN 

Synphetiyl  anisyl  ketoxime.,  Anisic  anilid. 

C6H5—  C—  C6H4(OCH3)      C6H5—  C  =  O 

II  —  II 

N—  OH  NHC6H4(OCH3) 

Antiphenyl  anisyl  ketoxime.  Benzoic  anisid. 

There  are  actually  known  among  the  stereoisomeric 
ketoximes  numerous  substitution  products  of  the  oximes 
of  benzophenone,  C6H5—  CNOH—  C6H4X,  such  as  the 
oximes  of  phenyltolyl  ketone,  and  of  phenylxylyl  ketone 
of  parachlor-,  brom-,  iodo-,  oxy-  and  amidobenzophenones, 
and  some  ortho  and  meta  derivatives  ;  besides  these  are 
two  monoximes  of  benzil,  C6H5CNOH—  CO—  C6H5, 
and  of  hydrobenzoin,  C6H5CNOH—  CHOHC6H5.  If 
the  fluid  ketoximes  of  the  fatty  series, 


are  transformed  into  amids,  they  behave  as  a  mixture 
of  two  isomers,  but  as  a  rule,  it  has  been  impossible  to 
isolate  the  two  modifications. 

On  the  other  hand,  the  oximes  of  benzoylpropionic,  or 
of  phenylketoximepropionic  acids, 

C6H5CNOH.CH2CH2COOH, 

of  which  two  stereoisomers  are  known,  contain  both  an 
aromatic  and  aliphatic  radical,  and  the  stereoisomeric 
oximes  of  oximidosuccinic, 


150  ELEMENTS   OF   STEREOCHEMISTRY 

COOH— CNOHCH2COOH, 
and  oximidoethylsuccinic  acid, 

COOC2H5— CNOHCH2COOH 

contain  two  radicals  belonging  to  the  fatty  series. 
Numerous  methods  of  determining  the  configuration  of 
these  compounds  have  been  used.  The  most  striking 
relies  on  the  transformation  of  derivatives  (2)  into 
nitrile  succinic  ester, 

COOC2H5— C— CH2COOH 

II 

HO— N 
i. 

COOC2H5— C— C  H2COOH 

II 
N— OH 

ii.  COOC2H5— C— CHCOOC2H6 

ll/ 

N 

in. 

Stereoisomeric  derivatives  of  hydroxamic  (hydrox- 
imic)  acids. — It  has  been  placed  beyond  doubt  that  many 
of  the  curious  physical  isomers  discovered  by  Lessen 
belong  to  the  stereoisomers  of  nitrogen.  This  is  the  case 
with  the  <*-and  ft-  ethylbenzhydroxamic  or  ethylbenz- 
hydroximic  acids,  C6H5— CNOH  -OC2H5.  The  configu- 
ration of  these  compounds  corresponds  to  the  following 
formulae  : 

C6H5-C-OC2H5         C6H5-C-OC2H5 

II  II 

HO— N  N— OH 

Syn  acid.  Anti  acid. 

For  the  first  alone  gives  phenylurethane  (according  to 
Beckmann's  reaction) 


GEOMKTRICAI,   ISOMKRISM  151 

C6H5— C— OC2H5      HO— C— OC2H5 

II  -~  II 

HON  C6H5— N 

OC2H5 
0=C-OC2H5  / 

|  or     C  =  O 

C6H5.H.N  \ 

NHC6H5 

while  the  second  leads  to  completely  different  derivatives, 
on  account  of  the  immobility  of  the  group  OC2H5.  The 
nonsubstituted  hydroximic  acids  are  not  yet  known  in 
stereoisomeric  forms,  probably  because  the  passage  from 
one  configuration  to  another  is  effected  so  easily  by  the 
intermediate  tautomeric  form 

NH(OH) 

/ 

C6H5C 

% 

O 

which  is  the  same  whatever  be  the  original  configuration. 

Stereoisomeric  dioximes  or  glyoximes. — These  sub- 
stances can  exist  in  three  modifications  with  a  symmetrical 
formula 

R— CNOH— CNOH— R  ; 

these  three  modifications  are  designated  respectively  by 
the  prefixes  anti-,  amphi- and  syn-,  corresponding  to  the 
formulae 

R— C— C-R  R— C— C— R 

I  II         II  2  ||         i| 

HO— N    N— OH  NOH     NOH 

Antiglyoxime.  Amphiglyoxime. 

R— C CR 

3        II  II-  • 

N— OH  HO— N 
Synglyoxime. 


152  ELEMENTS   OF   STEREOCHEMISTRY 

The  three  dioximes  of  benzil  (diphenylglyoximes), 
C6H5— CNOH.C.NOHC6H5,  correspond  to  these  three 
configurations,  while  the  dioximidosuccinic  or  glyoxime 
dicarboxylic  acids,  COOH.CNOH.CNOHCOOH,  of 
which  only  two  isomers  are  known,  will  be  represented  by 
formulae  (i)  and  (3). 

The  unsymmetrical  glyoximes  which  should  give  four 
modifications  are  only  known  as  yet  in  three  different 
forms.  To  this  group  of  compounds  belong  the  three 
monophenyl  glyoximes,  C6H5.CNOH.CNOH.N,  the 
chlordioximes,  and  the  glyoxime  monocarboxylic  acids, 
Cl.CNOH.CNOH.H,  of  which  two  isomeric  modifications 
are  known,  and  lastly,  the  methyl-  and  phenylglyoxime 
carboxylic  acids,  COOH.CNOH.CNOH.H,  and  methyl 
and  phenyl  glyoxime  carboxylic  acids,  of  which  two 
isomers  only  have  been  isolated  in  the  form  of  esters, 
acetates,  and  salts. 

Stereoisomeric  quinonoximes  have  recently  been 
obtained  ;  e.  g. ,  two  more  oximes  of  orthochlorquinone, 
each  giving  a  benzoyl  derivative,  and  two1  acetates  of 
quinone  dioxime.  This  last  corresponds  to  the  two 
formulae  : 

OAc 
I 
N=C6H4=N  N=C.H  =N 

I  ! 

OAc  OAc  OAc 

Determination  of  configuration. — The  configuration  of 
these  compounds  may  be  established  either  by  means  of 
the  preceding  methods  or  by  reactions  which  hold  good 
for  each  particular  case.  Thus  the  more  stable  of  the 
three  dioximes  of  benzil  can  be  transformed  into  oxani- 

1  Behrmann  :  Ber.  d.  chem.  Ges.,  27,  217;  28,  341. 


GEOMETRICAL   ISOMERISM  153 

lid  in  the  same  way  that  the  simple  quinoximes  gave 
amids.  Hence  this  oxime  is  antidiphenylglyoxime. 

C6H-C-C-C6H5 

HO— N     N— OH 

HO— C— C— OH  OC CO 

II      II  =  I 

C6H5N    N— C6H5  C6H5N.H  H.N.C6H5 

Antiglyoxime  dicarboxylic  acid  is  decomposed  by 
means  of  acetic  anhydrid  into  carbon  dioxid,  and 
cyanogen  as  are  the  aldoxime  carboxylic  acids  with  an 
analogous  configuration, 

COOH— C— C— COOH       C02         C— C       CO2 

II      II  +    III    III  + 

HO— N     N— OH  H2O         N    N       H2O 

the  syn-glyoximes  in  which  the  two  hydroxyl  groups  are 
in  apposition,  have  the  property  of  giving  anhydrids, 
azoxazols  or  furazans,  respectively, 

R_C C— R  R— C C— R 

II  II          =  H20  +          ||  || 

NOH    HON  N— O— N 

the  synglyoximes  are  also  produced  by  the  reduction  of 
the  glyoxime  peroxids,1 

R— C C— R  R— C CR 

II  II          +  H2  =         ||  |j 

N— O— N  N.OH  HON 

c.  Transformation  of   stereoisomers  into  one  another. 

— According  to  their  configuration  the  isomeric  oximes 
possess  a  stability  which  is  different  in  each  case.  It 
may  be  imagined  that  the  radicals  united  to  carbon, 
exercise  a  greater  or  less  attraction  on  the  oximic 

1  Angeli :  Gazz.  chim.  ital.,  22,  450. 


154  ELEMENTS   OF   STEREOCHEMISTRY 

hydroxyl,  which  should  depend  on  their  electropositive 
or  electronegative  character,  and  on  their  relative 
spatial  position.  Hence,  the  changes  in  the  configuration 
of  an  oxime,  are  dependent  on  the  same  cause  as  that  met 
with  in  the  ethylene  derivatives,  but  with  this  difference, 
that  they  change  much  more  readily.  This  explains  why 
the  isolation  of  the  two  stereoisomers  is  not  always 
possible. 

Transformations  taking  place  under  the  influence  of  heat. 
— The  action  of  heat  always  induces  the  transformation 
of  the  unstable  modification  of  the  oxime  into  the  stable 
form,  and  even  in  certain  cases  this  change  takes  place 
more  or  less  rapidly  at  ordinary  temperature,  leading  to 
a  complete  transformation,  or  to  a  state  of  equilibrium 
between  the  two  oximes,  e.  g. , 

C6H5-C-C6H4OH  C6H5-C-C6H4OH 

II  —  II 

N— OH  HO— N 

By  heating. 
Synparabenzophenonoxime.  Antiparaoxybenzophenoneoxime. 

C6H5— C—  COOH  C6H5— C— COOH 

II  —  II 

HO— N  N— OH 

Gradually.         Spontaneously. 

Antiphenylketoxitne  Synpheuylketoxime 

carboxylic  acid.  carboxylic  acid. 

If  the  temperature  be  raised,  and  if  it  produce  an  intra- 
molecular change,  one  obtains  the  same  substances,  no 
matter  which  of  the  oximes  be  employed.  This  takes 
place  in  quite  the  same  way  as  in  the  case  of  maleic 
anhydrid,  which  is  obtained  equally  as  well  in  starting 
from  fumaric  acid  as  from  maleic  acid.  The  modification 
which  is  not  directly  decomposed  is  transformed  probably 


GEOMETRICAL   ISOMKRISM  155 

first  of  all  into  its  isomer.  In  this  way  one  may  account 
for  the  formation  of  benzonitril  by  the  distillation  of  the 
antibenzaldoxime  acetate, 

C6H5-C-H  C6H-C        H 

II  111+   ! 

CH3COO— N^  N       COOCH3 

C6H— C-H 

II  / 

N— O— OC— H3 

Transformation  taking  place  with  the  aid  of  chemical 
reagents — These  transformations  are  very  numerous,  and 
are  accomplished  sometimes  by  simply  contact  action, 
but  more  frequently  with  the  formation  of  intermediate 
products,  which  as  in  theoximes,  the  metallic  compounds, 
compounds  with  acids,  or  in  some  cases  with  dibromids, 
the  nitrogen  atom  behaves  as  pentavalent.  These 
results  evidently  depend"  on  different  conditions  of  molec- 
ular stability,  but  it  must  not  be  forgotten  that  the 
terms  stable  and  unstable  refer  only  to  the  oximes  in  a 
free  state,  and  that  they  are  more  or  less  relative.  Thus, 
the  syn-  and  antialdoximes  of  the  aromatic  series  can 
give,  when  treated  with  dry  hydrochloric  acid,  the  cor- 
responding hydrochlorids, 

C6H5— C— H  C6H5— C— H 

<0  II  (2)  II 

HO— N— Cl  Cl— N.OH 


H 

Conversely  however,  with  the  free  oximes,  the  anti- 
hydrochlorid  is  unstable,  while  the  syn  derivative  is 
stable.  This  will  explain  why  by  the  molecular  trans- 
position, induced  by  hydrochloric  acid  gas,  one  may  pass 
from  the  anti  series  to  a  derivative  of  the  syn  series. 


UNIVERSITY 


156  ELEMENTS   OF  STEREOCHEMISTRY 

The  transformations  of  the  stereoisomeric  oximes  under 
the  influence  of  chemical  reagents  conform  to  certain 
general  rules.  A  change  in  the  constitution  can  hence 
modify  the  configuration  and  the  stability  of  the  isomers. 
The  following  scheme  will  give  a  general  resume  of  these 
different  transformations.  The  symbol  X  denotes  for 
example,  Na,  and  the  symbol  R  the  groups  (CH3.CO)  : 

Stable.  Unstable. 

R'  —  C  —  R"     Change  in  constitution         R'  —  Q  —  R" 


X-N  XO-N 

I  r 

'—  C—  R"        „.  t.t  f.          R'—  C—  R"  p§ 

|,  .          Change  in  constitution  .  (  g, 

A  +-:  -----  ||  03 

N—  OH  N—  OX    ? 

Unstable.  Stable. 

It  will  be  seen  according  to  this  figure,  that  it  is  more 
or  less  easy  to  obtain  oximes  of  a  given  configuration,  for 
there  is  for  each  oxime  a  stable  configuration  in  an  alka- 
line medium,  which  will  correspond,  for  instance,  to  that 
of  the  sodium  derivatives,  and  also  a  stable  configuration 
in  acid  media  which  correspond  to  an  hydrochlorid,  or 
to  an  acetyl  derivative.  Hence,  one  of  these  isomers  will 
be  formed  in  the  greater  quantity  or  even  completely, 
according  as  the  hydroxylamin  reacts  in  an  acid  or  an 
alkaline  medium.  Thus,  for  example,  for  the  different 
stereoisomeric  glyoximes, 

R'—  C.  NOH—  CNOH—  R" 

(oximes  of  benzil,  phenylglyoxal,  chlorgly  oximes,  gly- 
oxime  carboxylic  acids),  one  will  obtain  the  following 
relations  : 


GEOMETRIC AI<   ISOMERISM  157 

R— C— CNOHR"          R'— C— CNOHR" 

(I)  II  (2)  || 

HO— N  N— OH 

Stable  modification  in  acid      Stable  modification  in  alkaline 
solutions.  solutions. 

The  glyoximes  corresponding  to  formula  2  will  always  be 
formed  when  hydroxylamin  reacts  in  a  markedly  alkaline 
solution ;  these  glyoximes  treated  with  acids  are  trans- 
formed into  oximes  corresponding  to  formula  i .  This  last 
reaction  is  effected  more  or  less  easily.  Sometimes  a 
strong  acid  such  as  hydrochloric  acid  is  necessary,  at 
other  times  the  transformation  takes  place  so  easily  that 
in  order  to  isolate  the  oxime  which  has  been  formed  in 
an  alkaline  medium,  it  is  necessary  to  set  it  free  with 
carbon  dioxide. 

Similar  relations  exist  between  the  isomeric  oximes  of 
paraoxybenzophenone  and  phenylglyoxalic  acid.  These 
may  be  represented  by  the  following  figures  : 

C6H5— C— C6H4OH     NaOH     C6H5— C— C6H4OH 

ii  n  ii 

HO— N  HC1  N— OH 

C6H5— C-COOH         HC1       C6H5— C— COOH 

||  ^  | 

HO— N  NaOH  N— OH 

In  agreement  with  this,  the  oximes  which  are  unstable 
in  the  free  state  are  still  more  so  in  the  form  of  acetyl 
derivatives,  and  accordingly  the  introduction  of  an  acetyl 
group  by  means  of  acetic  anhydrid  is  performed 
usually  without  a  change  in  configuration,  while  if  one 
use  acetyl  chlorid,  the  hydrochloric  acid  disengaged 
induces  a  speedy  molecular  rearrangement. 

d.  Configuration  of  oximes  of  which  two  stereoisomers 
have  not  been  isolated. — The  unsymmetrical  oximes 
which  have  up  to  the  present  been  discovered  only  in  a 


158  ELEMENTS   OF   STEREOCHEMISTRY 

single  isomeric  modification  should  always  be  represented 
by  one  of  the  two  possible  configurations.  This  has 
already  been  mentioned  in  speaking  of  the  ethylene  com- 
pounds (see  p.  89).  When  it  is  impossible  to  isolate 
the  two  modifications  it  must  be  assumed  that  one  of  the 
configurations  is  particularly  unstable,  and  if  one  com- 
pare this  single  oxime  with  stereoisomers  having  an 
analogous  constitution  and  whose  configuration  is  known, 
one  may  find  that  by  these  chemical  and  physical  proper- 
ties it  conforms  closely  to  one  of  the  isomers,  and  differs 
completely  from  the  other. 

But  one  oxime  of  pyruvic  acid  and  of  thienylglyoxylic 
acid  have  been  isolated ;  the  aldehyds  of  the  fatty  series 
gives  but  one  oxime  ;  all  these  compounds  must  hence  be 
synaldoximes  and  synaldoximecarboxylic  acids,  because 
they  bear  a  strong  resemblance  to  the  benzalsynaldoxime 
and  to  the  synbenzaldoximecarboxylic  acids,  and  are 
decomposed  into  water  or  CO2  and  a  nitril. 

v^jgXljj,,  _j- !       \-s      -ti 

II 
N— OH 

CH3— C— COOH  C4H3S— C— COOH 

II  and  || 

NOH  N— OH 

The  oximes   of  the   ortho-substituted  aromatic   alde- 
hydes, of  which  but  one  modification  has  yet  been  iso- 
lated,   have   properties   analogous   to  those  of   antiben- 
zaldoxime,  and  hence  one  assigns  to  them  the  same  con- 
figuration as  antialdoxime, 
R 
J 

C— H. 


HO— N 


GEOMETRICAL   ISOMERISM  159 

The  oximes  of  mixed  ketones  which  are  easily  decom- 
posed into  anilids  of  fatty  acids, 

0=C— CnH2n  +  I 

I 
C6H5.N.H 

have  the  configuration, 

C6H5 — C — CWH2M  + 1 

II 
HO— N 

the  /?-ketoximic  acids,  RCNOH.CH2.COOH  (oximes  of 
acetoacetic  and  benzoyl  acetoacetic  acids),  and  the 
/?-oximido  ketones,  R — CNOH.CH2COR,  are  only 
known  in  a  single  modification, 

R— C— CH2COOH  R— C=CH2COR 

I!  II 

N— OH  N— OH 

These  two  configurations  take  into  account  the  for- 
mation of  internal  anhydrids  derived  from  synoxazol. 

R— C— CH2COOH  R— C— CH2— CO 

II 

N— OH 
Synketoximeacetic  acid. 

R— C— CH2.CO.R 

II 

N— OH 

Synoximidoketone.  Synoxazol. 

Although  but  .one  isomer  of  these  different  compounds 
has  as  yet  been  prepared,  it  must  not  be  thought  im- 
possible to  isolate  the  second  modification,  despite  its 
instability.  For  example,  recently,  the  derivatives  of 
thiophene  antialdoxime, 


160  ELEMENTS  OF  STEREOCHEMISTRY 

C4H3S— C— H 

II 
HO— N 

have  been  obtained,  although  the  parent  compound  is  not 
stable  in  the  free  state  ;  in  the  same  way  the  existence  of 
antioenanthaldoxime  which  is  still  less  stable  appears  to  be 
beyond  doubt,  from  the  way  in  which  certain  of  its 
derivatives  behave.  Finally  Franchimont1  has  been  able 
to  prepare  two  isomeric  acetaldoximes. 

Influence  of  constitution  on  configuration. — The  influ- 
ence2 of  configuration  on  constitution  has  been  less 
studied  in  the  case  of  the  oximes  than  in  the  case  of  the 
ethylene  derivatives.  The  existence  and  intramolecular 
reactions  of  two  derivatives, 

R'— C— R"  R'— C— R" 

H  and  || 

HO.N  N— OH 

depend  to  such  an  extent  on  the  two  radicals  R'  and  R", 
and  occur  in  such  a  regular  way,  that  one  is  able  to 
systematically  classify  these  radicals  according  to  their 
affinity  for  the  oximidohydroxyl  and  to  predict  before- 
hand the  properties  of  an  oxime  of  a  given  constitution, 
if  one  knows  the  nature  of  the  two  groups  R'  and  R". 
This  can  be  classified  in  the  following  way  : 

i.  COOH.CH2— ,  2.  COOH— ,  3.  C6H5— ,  4.  C6H4H— , 
5.  C4H3S-,  6.  CWH2W+I— ,  7.  CH— . 

The  methyl  carboxyl  group  which  has  the  greatest 
affinity  for  the  oxime  hydrogen,  stands  at  the  head  of  the 
list.  The  group  with  the  lowest  affinity  for  the  hydrogen, 
is  the  hydrocarbon  radical  methyl.  Among  all  the 
alkyl  radicals  it  is  this  last  which  has  the  weakest 

1  Franchimont :  Rec.  trav.  Pays  Bas.,  10,  236. 

2  Hantzsch  :  Ber.  d.  chem.  Ges.,  15,  2164. 


GEOMETRIC AI,   ISOMKRISM  l6l 

affinity  for  the  oximidohydroxyl.  According  as  the 
hydroxyl  will  be  more  or  less  remote  from  the  latter,  one 
may  deduce  the  stability  of  the  following  compounds  : 

COOHCH2— C— R  COOHCH2— C— R 

ll  II 

HO— N  NOH 

Very  stable.  Very  unstable,  not  isolated. 

CH3— C— R  CH3— C— R 

II  II 

HON  N.OH 

Very  stable.  Very  unstable,  not  isolated. 

The  stability  of  these  two  compounds  is  then  more  or 
less  modified  by  the  nature  and  position  of  the  radical  R. 
Gradual  transformations  which  go  to  substantiate  this 
stability  are  particularly  well  marked  in  the  group  of 
oximes  of  the  general  formula,  C6H5— CNOH— R,  R, 
representing  respectively  the  above-mentioned  radicals. 

Oximes,  C6H5— CNOH— R. 

1.  R^CH2COOH     C6H5— CNOH— CH2COOH 

Synphenylketoxime  acetic  acid. 
(Oximes  of  benzoyl  acetic  acid). 

a.   C6H5— C— CH.2COOH      b.  C6H5— C— CH2COOH 

II  II 

N— OH  HO.N 

Synphenylketoxime  acetic  acid.  Antiphenylketoxime  acetic  acid. 
Known,  very  stable.  Unknown 

2.  R-=COOH  C6H5— CNOH— COOH 

Phenylketoxime  carboxylic  acid. 
(Oxime  of  phenylglyoxylic  acid.) 

a.  C6H5— C— COOH  b.  C6H5— C— COOH 

II  il 

N— OH          f  HON 

Synphenylketoxime  carboxylic  Antiphenylketoxime  carboxylic 

acid.     Stable.  acid.     Unstable, 

ii 


1 62  ELEMENTS   OF   STEREOCHEMISTRY 

3.  R= C6H4X  C6H6— C— C6H4X 

Oximes  of  substituted  benzophenones. 

C6H5-C-C6H4X  C6H5-C-C6H4X 

N— OH  HO— N 

Usually  unstable.  Usually  stable. 

A  greater  or  less  stability  of  these  oximes  depends 
besides  on  the  nature  of  the  substituent  X,  as  is  shown 
in  the  above-mentioned  table,  as  well  as  the  place  which 
it  occupies  in  the  benzene  nucleus,  or  in  other  words  on 
its  relative  remoteness  from  the  oximido  hydrogen.  The 
substituent  thus  exerts  a  more  energetic  action  in  the 
ortho  position  than  in  the  para.1 

R=CH3         C6H5— C— CH3 

HON 

Phenyl  methyl  ketoximes. 
Oximes  of  acetophenone. 

*C6H5-C-CH3         C.H— C— CHS 

II  II 

N— OH  HO— N 

The  influence  of  two  radicals  on  the  stability  of  oximes 
is  also  very  well  marked  in  the  case  of  their  compounds, 
as  for  example,  in  the  oximido  acids,  COOH — CNOH — R. 
If  one  replaces  R  in  the  latter  by  some  one  of  the  above 
mentioned  radicals,  one  has  a  series  in  the  following 
order  : 

COOH— C— CH2OH     COOH— C— COOH 

II  II 

HON  HON 

Unstable.  Stable. 

COOH— C— (C6H4X  or  C4H3S  or  CH3) 

II 

HON 
Very  stable. 
1  Smith  :  Ber.  d.  chem.  Ges.,  24,  4057. 


GEOMETRICAL   ISOMERISM  163 

In  the  anti  series  one  will  have  the  stability  occurring 
in  reverse  order. 

These  relations  have  to  a  very  large  extent  a  general 
character,  and  the  way  in  which  their  radicals  behave,  e.g. , 

(C6H5-COC1 

OC2H5— CN)  ' 

allows  one  to  place  them  in  the  table  on  p.  160,  although 
with  more  or  less  uncertainty.  Hydrogen  occupies  an 
independent  position  in  this  table  as  will  be  seen  when 
one  has  indicated  the  properties  of  the  aldoximes  clearly. 
According  to  the  configuration  of  aldoxime  acetic  acid, 

H-  -C— CH2COOH 

HO— N 

hydrogen  should  be  placed  at  the  head  of  the  list  of 
radicals,  but  as  the  aromatic  aldoximes,  especially  those 
of  the  ortho  series,  are  stable  in  the  inverse  configuration, 

H— C— C6H5(or  C6H,X) 

I! 

N— OH 

it  is  necessary  on  the  contrary,  to  place  hydrogen  after 
the  aromatic  radicals.  This  peculiar  influence  of  the 
hydrogen  atom  on  the  configuration  depends  perhaps  on 
its  small  size,  and  its  relatively  great  mobility.  These 
properties  have  already  been  ascribed  tQ  it  in  the  study 
of  the  tautomerism  of  hydrogen  compounds.  It  is  thus 
seen  that  the  two  radicals  R'  and  R"  determine  not  only 
the  stability  of  the  configuration  but  also  the  chemical 
characteristics,  and  allow  the  prediction  of  the  intra- 
molecular reactions  which  depend  solely  on  the  relative 
distance  of  the  atoms  making  up  the  complex.  It 
suffices  thus  to  allow  that  in  molecules,  such  as 


1 64  ELEMENTS   OF   STEREOCHEMISTRY 

R'— CNOH— R", 

the  absolute  distance  of  the  oximido  hydroxyl  from  the 
two  radicals  depends  on  their  reciprocal  affinities  and 
their  more  or  less  electropositive  or  electronegative  char- 
acter, as  will  be  seen  by  referring  to  the  table  on  p.  160. 
If,  for  example,  R'  represent  a  group  having  a  strong 
affinity  for  hydroxyl  and  R"  a  group  possessing  a  feeble 
attraction  or  even  a  repulsion,  the  two  configurations 
may  be  perhaps  represented  in  the  following  manner : 

R'— C— R"  R'— C— R" 

HO\   ||  and  || 

XN  N 

\ 
OH 

If  then  in  the  case  of  oximes  that  the  analogous  con- 
stitution radical  R,  which  is  situated  near  the  hydroxyl, 
reacts  in  the  following  manner  : 

R'— C— R"  R'— C  K' 

II  III        +        I 

N— OH  N  OH 

and  if  without  changing  R",  one  replace  R'  successively  by 
the  different  groups  in  the  table  on  page  160,  the  mechan- 
ism of  this  intramolecular  action  will  be  greatly  modified  in 
the  following  manner  :  If  the  varying  radical  R'  is  one  of 
the  latter  terms  of  the  series,  the  attractive  action  which 
it  exercises  on  hydroxyl  will  be  weak,  and  consequently 
the  radical  R"  will  attract  the  group,  OH,  with  greater 
force,  and  decomposition  will  take  place  more  readily.  If, 
on  the  contrary,  the  group  R  represents  one  of  the  first 
members  of  the  series,  it  will  tend  to  attract  this 
hydroxyl  from  the  sphere  of  influence  of  the  group  R", 
and  the  reaction  mentioned  above  will  not  take  place,  or 
if  it  does,  will  take  place  to  a  limited  extent  only. 


GEOMETRICAL   ISOMERISM  165 

The  transformation  of  the  synaldoximes  and  their  acids 
into  nitriles,  examples  of  these  : 

R'— C— H  R'— C  H 

II  —  III       +    I 

N— OH  N  OH 

R'— C— COOH  R'— C  COOH  ' 

II  —  III     +      I 

N— OH  N  OH 

This  reaction  proceeds  easily  if  R'  =  CH3  and  CWH2W  +  I; 
hence  the  acetates  of  acetaldoxime  and  its  homologues 
and  the  oxime  of  pyruvic  acid  are  decomposed  sometimes 
spontaneously  at  ordinary  temperature.  When 

R'  =  C4H3S 

(thiophenealdoxime  and  the  oxime  of  thienylglyoxylic 
acid),  if  R'  —  C6H5  (synbenzaldoxime  and  the  oxime  of 
phenylglyoxylic  acid) ,  the  acetates  are  still  more  stable ; 
lastly  if  R'  =  CH.COOH  (aldoxime  acetic  acid  and 
oximido  succinic  acid  or  synketoxime  acetyl  carboxylic 
acid),  the  acetates  no  longer  react  the  same,  in  spite  of 
their  identical  configuration.  The  capability  of  reacting 
differently  in  these  compounds  is  shown  by  the  following 
symbolic  formulae  which  are  given  concretely  as  a  result 
of  the  study  of  the  thiophene  compounds, 

CH3— C— H  (or  COOH )     C6H5— C— H  or  COOH 
II  /OH  || 

N/  N— OH 

COOHCH2— C— H  (or  COOH) 

II 

N\ 

XOH 

This  is  the  same  for  the  most  part  in  intramolecular 
reactions  ;  for  example,  in  the  formation  of  anhydrids 
(derivatives  of  oxazol),  starting  from  /3-ketoxime  acids 


1 66  ELEMENTS   OF   STEREOCHEMISTRY 

and  oximido  ketones  which  may  be  represented  by  the 
following  formulae  : 

CH3— C— CH2COOH  (orCH2.CO.R) 
>H 


I!  /oi 

N/ 


and 

COOH— C— CH2COOH  (or  CH2COR) 

N\ 

X)H 

If  one  replace  the  radical  R  in  the  group  R — CNOH, 
by  the  group  CH3,  the  anhydrids  are  formed  easily,  and 
on  the  other  hand,  with  much  difficulty,  or  even  not  at 
all,  if  the  radical  R  be  replaced  by  COOC2H5. 

The  groups  which  are  not  participating  in  the  reaction 
always  act  in  the  same  way  at  the  moment  of  intra- 
molecular decomposition,  and  the  absolute  configuration 
is  modified  according  to  previous  relations  deduced  from 
the  table  on  page  160.  In  all  these  cases,  the  alcoholic 
radicals  exercise  the  same  influence  as  that  which  was 
observed  in  the  group  of  ethylene  compounds,  and  as  a 
general  rule,  favor  intramolecular  decomposition.  Their 
constitution  ought  thus  to  be  taken  into  consideration,  if 
one  wishes  to  form  some  idea  of  their  relative  influence 
on  intramolecular  decomposition.  It  would  appear  that 
this  is  in  close  connection  with  their  molecular  con- 
ductivity, and  K,  their  constant  of  affinity.  This 
constant  which  was  studied  in  the  homologous  series  of 
the  tf-ketoxime  carboxylic  acids, 

CnHan  +  x— CNOH— COOH, 

does  not  decrease  when  n  augments,  but  conversely  to 
that  which  is  found  in  the  melting-points  of  certain 
classes  of  acids  which  increase  and  decrease  alternately; 


GEOMETRICAL   ISOMERISM  167 

the  differences  become  less  and  less  great.  This  would 
tend  to  show  that  the  carboxyl  group  always  exerts  the 
greatest  attraction  for  the  oximido  hydrogen.  This 
attraction  is  strongly  compensated  by  hydrogen,  much 
less  by  methyl ;  ethyl  acts  somewhat  more  markedly  than 
methyl,  and  propyl  less  than  ethyl.  This  is  shown  in 
the  following  figures  : 

-  H— C— COOH  CH3— C— COOH 
II  II    /OH 

Nx  N< 

X)H  K  =  0.0514 

K  =  0.0995  C3H7— C— COOH 
C2H5— C— COOH  ||    /OH 

I!  N/ 

Nv  K  =  0.0685 

XOH 
K  =  0.0830 

The  affinity  constant,  of  the  stereoisomeric  oximido 
acids  vary  between  the  same  limits  as  in  the  ethylene 
carboxylic  acids,  but  they  also  present  differences  varying 
with  the  distance  which  separates  the  two  groups  NOH 
and  COOH. 

R— C— COOH  R— C— COOH 

II  II 

HO— N  Stronger.  N — OH      Weaker. 

Stereoisomeric  and  ketoximic  acids. 

R— C— CH,COOH  R— C-COOH 

II  II- 

HO — N  Stronger.  N— OH        Weaker. 

Stereoisomeric  /3-ketoximic  acids.] 

R-C— CH2CH2COOH         R— C— CH2CH2COOH 

II  II 

HO— N  Stronger.  N— OH          Weaker. 

Stereoisomeric  7-ketoximic  acids. 

The  affinity  constant  analogous  to  the  ketoxime  acids 


1  68  ELEMENTS   OF    STEREOCHEMISTRY 

increases  or  diminishes  for  each  addition  of  a  CH2  group. 
This  is  a  formulation  of  the  statement  given  on  page  122  ; 
viz.  ,  that  the  structural  formula  of  compounds  consisting 
of  long  chains  of  carbon  atoms,  does  not  express  the  real 
distance  between  the  atoms. 

The  isomerism  of  oximes  is  found  in  their  derivatives 
and  sometimes  in  the  salts  formed  with  hydrochloric 
acid  of  the  formula 

a  H 

\  / 

C=N—  OH, 


in  which  nitrogen  is  pentavalent,1  but  these  two  isomeric 
compounds  are  much  more  easily  transformed  one  into 
the  other  than  in  the  case  of  free  oximes. 
Stereoisomeric  hydrazones.  — 

a—  C—  b  a—C—6 

II  and  || 

R'—  R'N—  N  N—  NR'R" 

Cases  of  isomerism  of  this  kind  were  observed  first  in 
the  phenylhydrazone  of  orthonitrophenylglyoxylic  acid2 
which  exists  in  two  modifications,  and  independently  with 
hydrazones  obtain  in  a  single  modification,  starting  from 
the  ketones  a  —  CO  —  b.  These  hydrazones  are  obtained 
by  treating  ketonechlorids,  a  —  CC12  —  b,  with  hydrazins  ;3 
thus,4  in  this  group  of  compounds  there  are  two  mono- 
phenylhydrazones  of  anisylphenylketone, 

CH8OC6H4X 

XC=NNHC6H5, 


1  Proc.  Chem.  Soc.,  1893,  253. 

2  Fehrlin  and  Krause  :  Ber.  d.  chem.  Ges.,  23,  1574  and  3617. 

3  Hantzsch  and  Kraft  :  Ibid.,  24,  3511. 

4  Hantzsch  and  Overton  :  Ibid.,  26,  9  and  18. 


GEOMETRICAL   ISOMERISM  169 

and   two   diphenyldihydrazones   of   anisylphenylketone, 
and  of  tolylphenylketone, 

CH3O  or  CH3C6H4V 

>C=N-N(C6H5)2. 
C.H/ 

These  latter  compounds  are  particularly  interesting 
because  they  exclude  all  structural  differences  in  the 
hydrazone  group,  and  show  very  markedly  the  cause  of 
stereoisomerism  as  strictly  due  to  nitrogen.  The  follow- 
ing are  configuration  formulae  for  these  compounds : 

N02.  C6H4— C—COOH  N02.  C6H4— C—COOH 

II  II 

C6H5— NH— N  NC6H.C6H5 

Hydrazones  of  orthonitrophenylglyoxylic  acid. 

XC6H4— C— COOH  X.C6H4— C— COOH 

II  II 

C6H5— NH— N  N— NHC6H5 

Monophenylhydrazones  of  substituted  benzophenones. 

XC6H-C-C6H5  XC6H4-C-C6H5 

II  II 

(C6H5)2NH-N  N-N:(C6H5)2 

These  formulae  present  some  analogy  with  those  of  the 
stereoisomeric  oximes,  which  is  still  more  striking  when 
the  reciprocal  transformations  are  studied.  Thus,  by 
the  action  of  an  alkaline  solution,  the  isomer  of  the 
hydrazone  of  orthonitrophenylglyoxylic  acid  is  obtained. 
This  recalls  the  properties  of  the  *  oximes  of  phenyl- 
glyoxylic  acid.  There  is,  thus,  a  stable  modification 
which  is  the  antipode  of  that  observed  with  acids  in  speak- 
ing of  the  oximes,  and  a  stable  modification,  which  is  the 
reverse  of  that  seen  in  the  case  of  alkalies  acting  on  these ' 
last-mentioned  substances.  The  two  modifications  of 
the  hydrazones  of  asymmetric  ketones  are  not  equally 


170  ELEMENTS   OF   STEREOCHEMISTRY 

stable.  This  is  comparable  to  what  has  been  observed  in 
the  case  of  the  asymmetric  oximes, 

XC6H4— CNOH— C6H5. 

The  unstable  modifications  of  monophenylated  hydra- 
zones  melt  at  a  low  temperature,  are  soluble,  and  are 
transformed  into  less  soluble  modifications  which  melt  at 
a  higher  temperature,  and  this  takes  place  more  easily 
than  with  the  unstable  oximes.  This  reaction  takes 
place  at  room  temperature  when  an  alcoholic  solution  of 
hydrochloric  acid  is  used,  or  even  when  such  reagents  as 
acetyl  chlorid  or  anhydrid  are  allowed  to  act.  The 
stable  hydrazones  may  be  transformed  into  their  unstable 
modifications  by  treating  the  addition  products  formed 
with  acetyl  chlorid  with  dry  ammonia  gas.  This 
reaction  has  not  been  effected  in  the  case  of  diphenyl- 
ated  hydrazones. 

The  methods  mentioned  to  determine  the  configuration 
of  oximes  cannot  be  applied  to  the  determination  of  the 
configuration  of  hydrazones,  and  hence,  the  problem 
still  awaits  a  solution. 

The  two  modifications  of  diphenylsemicarbazid  and 
its  two  ethers  which  are  characterized  by  the  group 
(SCH3)C6H5NH—C(NNHC6H5)—SHCH3  should  be  clas- 
sified among  the  stereoisomerism  of  hydrazones.  These 
compounds  form  condensation  products  with  carbonyl 
chlorid  according  to  the  following  : 

C6H5.NH— C— SH  C6H5NH— C— SH 

II  II 

C6H5.NH— N  N— NH.C6H5 

and  subsequently  form  cyclic  compounds  of  different 
structure, 


GEOMETRICAL  ISOMERISM  171 


C6H5.  N— C— SH  C6H5— NH— C S 


OC 


/ 
\ 


and 


\ 


CO. 


C6H5N— N 


N— N.C6H 


This  reaction  is  not  effected  completely  with  the  second 
of  the  two  isoniers  ;  as  with  the  first,  two  condensation 
products  are  obtained,  the  one  representing  a  stable 
modification,  the  other  an  unstable. 

The  stereoisomeric  hydrazones  of1  salicylic  aldehyde 
have  recently  been  isolated ;  dioxysuccinic  esters  and 
phenylhydrazine  react  on  one  another  to  give  different 
oxazones,  according  to  the  formula, 

COOR— C(NH2C6H5)— C(NH2C6H5)— COOR, 

which  behave  like  the  symmetrical  dioximes  and  corre- 
spond to  the  three  :  Syn,  amphi,2  and  anti  configurations. 
Lastly  the  two  modifications  of  dimolecular  ethylidene 
anilins3  of  the  formula, 

2C6H5CH:NC6H5  =  C6H5CH:NHC6H5CH2CHNC6H5, 

must  be  considered  as  geometric  isomers  corresponding  to 
the  following  configurations  : 

CUHUN— C— H         CMHUN— C— H 

II  II 

C6H5-N  N-C6H5 

This  is  indicated  by  their  different  behavior,  and  in 
particular  by  the  possibility  of  transforming  the  more 
fusible  modification  into  the  higher  melting  compound. 

1  Bitz:  Ber.  d.  chem.  Ges.,  27,  2288. 

2  Anschiitz  and  Paulz  :  Ibid.,  28,  64. 

3  Miller  and  Plochl  :  Ibid.,  27,  1297. 


172  ELEMENTS   OF   STEREOCHEMISTRY 

IV.  NITROGEN  COMPOUNDS  EXHIBITING  GEOMETRICAL 
ISOMERISM 

i.  Stereoisomeric  diazo  compounds, 

C6H— N  C6H5-N 

II  II 

R-N  N— R 

a.  Historical.  The  identity  of  the  structural  formulae. 
— These  compounds  are  interesting  not  only  from  a 
chemical  point  of  view,  but  as  an  example  of  historical 
development.  Like  the  "  iso-oximes,"  the  isodiazo 
hydrates  were  considered  at  first  as  isomers,  which  were 
represented  by  different  constitutional  formulae. 
Schraube  and  Schmidt1  who  discovered  the  potassium 
salt  of  isodiazobenzene,  as  well  as  the  hydrate  of  nitro- 
isodiazobenzene,  regarded  these  compounds  as  primary 
nitrosamins,  C6H5— NKNO  and  NO2C6H4NHNO. 
Their  alkaline  salts  treated  with  alkyl  iodids  are  trans- 
formed into  secondary  nitrosamins,  C6H5N.CH3.NO,  and 
NO2C6H4NCH3NO.  Shortly  after  this,  Bamberger2 
described  isodiazonaphthalin  as  a  naphthylnitrosamin. 
In  opposition  to  this  view,  Hantzsch,3  in  bringing  for- 
ward the  analogy  which  exists  between  the  geometric 
isomers  of  nitrogen  and  carbon  (oximes),  and  the  com- 
pounds characterized  by  two  atoms  of  nitrogen,  doubly 
linked  (diazo  compounds),  showed  that  the  introduction 
of  an  alkyl  radical  into  a  diazohydrate  does  not  furnish 
any  indication  of  its  constitution  as  was  already  shown  in 
the  case  of  the  isooximes.  Hence,  this  reaction  might 
only  be  considered  as  an  argument  in  favor  of  tautom- 
erism,  for  the  same  isodiazo  hydrates,  transformed 

1  Ber.  d.  chem.  Ges.,  27,  514. 

2  Ibid.,  27,  679. 
8  Ibid.,  27,  701. 


GEOMETRICAL   ISOMERISM  173 

into  their  silver  salts,  give  true  oxy  esters  ;l  e.  g., 
NO2C6H5 — N=N — OCH3.  Moreover,  isomeric  salts  cor- 
responding to  the  formulae  C6H5 — N=N.OMe  and 
C6H5.NMe.NO,  would  constitute  an  absolutely  unique 
case  of  this  kind.  At  the  same  time,  Hantzsch2  brought 
forward  the  first  experimental  basis  for  the  stereo- 
chemistry of  diazo  bodies  by  isolating  the  salts  of  the 
diazosulfonic  acids,  R.N2.SO3Me,  and  shortly  after  the 
diazocyanid  compounds,3  R.N2.CN — compounds  which 
no  longer  contain  the  carboxyl  group  of  diazohydrates, 
but  in  which  the  two  isomeric  forms  present  the  same 
analogies.  On  the  other  hand,  the  synthesis  of  isodiazo- 
benzene  hydrate,  starting  from  nitrosobenzene  and  hy- 
droxylamin,4  showed  that  the  isodiazo  hydrates  are  true 
hydroxyl  compounds. 

Nevertheless,  an  attempt  has  been  made  to  explain 
these,  by  means  of  constitutional  formulae.  The  salts  of 
diazo  benzene  with  mineral  acids,  the  normal  metallic 
salts  of  the  sulfonic  acids,  and  the  cyanid  of  diazo- 
benzene  should,  in  accordance  with  an  interpretation  given 
by  Blomstrand  and  Erlenmeyer,  be  represented  by  formu- 
lae conforming  to  the  ammonium  type, 

C6H5N.X  C6H5N.(OMe.S03Me.CN), 

i.  Ill  n.  HI 

N  N 

while  the  isodiazo  salts  should  correspond  to  a  true  diazo 
formula, 

C6H5N  :  N(OMeS03MeCN). 

The  following  objection  has  been  raised  to  this  inter- 
pretation :  The  compounds  which  have  been  considered 

1  Pechmann  :  Ber.  d.  chem.  Ges.,  27,  672. 

2  Hantzsch  :  Ibid.,  27,  1276,  2099. 

3  Hantzsch  and  Schultze  :  Ibid.,  28,  266. 
*  Bamberger  :  Ibid.,  28,  1218. 


174  ELEMENTS   OF   STEREOCHEMISTRY 

as  derivatives  of  the  true  diazo  group,  form,  as  a  matter 
of  fact,  two  distinct  series  of  compounds  which  differ  with 
the  constitution  of  the  diazo  radical,  and  which  have  not 
been  confused  up  to  the  present,  although  they  are 
changed  very  readily,  one  into  the  other.  The  following 
is  a  resume  of  the  Hantzsch  theory  regarding  these  com- 
pounds : 

First,  the  salts  formed  by  diazo  benzene  with 
acids  should  be  represented  by  Formula  i .  By  reason  of 
their  analogy  with  ammonium  type,  one  may  assign  to 
them  the  name  diazonium.  Their  aqueous  solutions 
have  a  neutral  reaction,  and  are  as  completely  dissociated 
as  the  salts  of  potassium  and  ammonium.  Diazo  car- 
bonates are  also  known,  which  are  soluble  in  water,  also 
double  salts  which  are  less  soluble  and  are  colorless, 
which  properties  are  also  characteristic  of  potassium  and 
ammonium.  "  Diazonium  "  appears  then  to  behave  like 
a  compound  radical,  having  metallic  characteristics. 

Second,  salts  like  the  cyanid  and  the  sulfonate  of 
normal  diazobenzene  do  not  correspond  to  Formula  2, 
but  to  the  usual  formula,  C6H5N  :  NR,  only,  in  this 
group,  we  find  isomers  of  identical  structure;  viz.,  the 
isodiazo  compounds  which  must  be  distinguished  from 
the  normal  diazo  compound.  Hence,  since  diazonium 
should  be  regarded  as  a  compound  alkali,  this  radical 
cannot  give  at  the  same  time  alkaline  salts  and  salts  of 
silver.  One  can  no  longer  explain  why  the  colorless 
sulfonic  compounds  with  the  group  N.SO3Me,  are 
transformed  into  cyanids,  absolutely  different  from  all 
cyanids  known,  corresponding  to  the  ammonium  type. 
The  diazonium  cyanid  should  be  colorless,  soluble  in 
water  dissociating  into  its  ions,  as  do  the.  different 
cyanids  of  ammonium,  or  of  tetramethyl  ammonium  ;  but 


GEOMETRICAL   ISOMERISM  175 

as  is  well  known,  diazonium  cyanid  is  colorless,  is  insolu- 
ble in  water,  and  is  a  bad  electrolyte.  Lastly,  the  normal 
and  isodiazo  compounds  present  strong  analogies  to  those 
properties  which  exist  in  the  geometric  isomers  of  the 
ethylene  group  and  of  the  oximes.  It  would  hence  be 
impossible  to  attribute  to  one,  an  ammonium  structure, 
and  to  the  other,  a  structure  like  that  of  the  azo  com- 
pounds. As  is  even  the  case  with  stereoisomers,  they 
are  characterized  by  special  intramolecular  reactions;  i.  e., 
by  their  capability  of  reciprocal  transformation.  These 
two  series  of  compounds  corresponding  to  the  single 
formula  C6H5N=NX,  can  then  be  designated  by  the 
names,  syndiazo  and  antidiazo.^ 

In  spite  of  the  very  marked  differences  between  the 
derivatives  of  diazonium  and  the  syndiazonium  com- 
pounds there  are  very  close  relations  between  these  two 
groups  of  compounds.  To  sum  up  what  has  been  men- 
tioned in  these  two  paragraphs  : 

Third,  the  diazonium  salts  are  transformed  easily  into 
normal  diazo  compounds.  It  will  be  seen  further  on  that 
the  latter  correspond  to  the  syn  configuration.  This 
reaction  can  then  be  expressed  by  the  following  : 

f  R  C6H5R 

N  =  N  +    i  =        |        |    -f  XHMe. 
I                   H(Me)  N  =  N 

X 

A  striking  example  of  a  transformation  of  this  kind  is 
furnished  by  diazosulfonic  acid.  The  free  acid, 

C6H5/  ^3\0  , 

has  all  the  properties  of  a  salt.     Its  reaction  is  neutral 


176  ELEMENTS   OF  STEREOCHEMISTRY 

and  like  the  compound  betain,  which  is  an  internal  salt 
of  ammonium,  this  acid  is  an  internal  salt  of  diazonium. 
If  a  molecule  of  alkali  be  added,  the  solution  which  is 
strongly  alkaline  at  the  beginning,  becomes  gradually 
neutral.  It  thus  contains  the  salt, 

,N2OH 
C6J 


But  the  salt  of  diazonium  is  transformed  into  the  syn- 
diazo  complex,  otherwise  one  could  not  understand  how 
a  solution  of  an  acid  which  was  originally  neutral,  could 
regain  its  neutral  reaction  after  the  addition  of  an 
alkali. 

b.  The  properties  and  methods  of  formation  of  the 
stereoisomeric  diazo  compounds. — In  the  group  of  stereo- 
isomers  corresponding  to  the  formula,  R.N:N.X,  there 
are  at  present  known  : 

First,  the  metallic  salts  of  diazobenzene,  among  these 
the  alkaline  and  silver  salts.  These  two  series  of  isomers 
are  colorless  ;  in  aqueous  solution  the  alkaline  salts  are 
electrolytically  dissociated ;  the  salts  of  silver,  however, 
undergo  hydrolysis.  From  this  point  of  view  they 
behave  like  the  stereoisomeric  salts  of  the  benzaldioximes. 

Second,  the  diazosulfonic  salts,  RN2SO3Me.  The  two 
series  of  salts  give  strongly  colored  solutions. 

Third,  the  diazo  cyanids,  R — N2CN.  The  two  series 
of  salts  dissolve  only  in  organic  media.  In  both  groups 
the  substances  are  colorless,  which  is  in  conformity  with 
what  one  would  expect  from  their  constitution. 

The  normal  diazo  salts  are  formed  by  starting  from  the 
diazonium  salts  by  the  interaction  of  alkalies,  silver  oxid, 
and  sulfite  or  cyanid  of  potassium. 


GEOMETRICAL   ISOMERISM  177 

•o 

OK/S03KCN\        R       OK(S03K.CN) 
NEEN+  |  .  I    |          |      I  ==    |         |  -f  KC1. 

|  K   \K        K    /        N^N 

Cl 

The  isodiazo  salts  are  formed  by  the  molecular  rearrange- 
men  t  of  the  syn  compounds.  The  less  stable  syn  com- 
pounds pass  into  the  more  stable  antiderivatives, 

R— N  R— N 

II      —  II 

(CN.S03K.OK)— N  N— (OKS03KCN) 

The  less  stable  syn  isomers  are  more  soluble  than  the 
more  stable  anti  isomers.  This  is  in  agreement  with 
what  was  found  in  the  case  of  the  cis  and  trans  compounds 
of  ethylene. 

c.  Determination  of  configuration. — i.  By  means  of  in- 
tramolecular reactions. — According  to  the  principle  which 
governs  intramolecular  actions,  the  syn  compounds  alone 
can  be  decomposed  with  the  disengagement  of  diazo  ni- 
trogen. 

C'H-!?      -       T'  + 1 

R— N  R  N 

The  normal  diazo  compounds  thus  conform  to  the  syn 
configuration. 

Examples  :  The  diazo  salt  of  sulfanilic  acid,  KOSO2. 
C6H4N2.OH,  is  transformed  at  ordinary  temperature  into 
nitrogen  and  potassium  phenolsulfonate, 

KOSO2— C6H4— N  KOSO2.C6H4        N 

II     —  I      -Mil- 

HON  OH  N 

The  syndiazo  cyanids,  or  normal  diazo  cyanids  are  con- 


178  ELEMENTS   OF  STEREOCHEMISTRY 

verted  in  like  manner  into  nitrogen  and  cyanids  by  means 
of  finely  divided  copper. 

C1.C6H4N  C1C6H4         N 

II  —  I         +    III 

NC— N  CN  N 

The  isodiazo  or  antidiazo  compounds  are  not 
decomposed  directly  with  the  formation  of  nitrogen. 
They  return  to  the  syn  type.  In  direct  decompositions, 
they  do  not  give  a  compound  free  from  nitrogen,  (RX), 
and  substances  containing  two  atoms  of  this  element, 
but  rather  two  derivatives,  each  containing  an  atom  of 
nitrogen.  Examples :  The  hydrate  of  nitroantidiazo- 
benzene  is  transformed  on  boiling  with  water  into 
nitranilin  and  nitrous  acid, 

N02C6H4N  H2 

||  +       |    =  C6H4.NH2.N02+HN02. 

NOH      ' .     O 

The  decomposition  of  secondary  nitrosamins  may  be 
explained  by  regarding  them  as  alkyl  derivatives  of  anti- 
diazo hydrates, 

R-N  R— N— CH3  R.NH.CH3 

II  ^  ^  I  »_>  | 

N— OK  NO  HN02 

It  will  be  noticed  that  the  diazonium  derivatives  often 
react,  apparently  at  least,  as  true  diazo  derivatives.  The 
transformations,  therefore,  are  not  direct  as  the  following 
equation  would  indicate, 

C6H5N— N  N 

HI          +C.H.X+IH, 

N  N 

but  are  indirect,  in  the  sense  that  they  form  a  syndiazo 
compound,  which  is  frequently  exceedingly  unstable. 


GEOMETRICAL   ISOMERISM  179 

This  is  what  should  be  understood  when  phenol  is  formed 
by  boiling  benzene  diazonium  chlorid  with  water, 

C6H5  p  TT       QTT  C6H5OH 

|  OH  ^  |5 

NEEN  +  -          J^i       -      N  =  N. 

i  +  H— C1  C1±H 

Similarly  in  the  formation  of  benzene  and  the  ethyl 
ester  of  phenol  by  boiling  the  same  chlorid  with  alcohol, 
the  syndiazo  ester, 

CeH5  OC.H, 

» 

N  —  N 

produced  as  an  intermediate  product  in  the  reaction,  can 
in  reality  be  decomposed  in  two  ways  : 

C6H5— N  C6H.  N        or        C6H6          N 

I      -       I  +111  +|||. 

C2H50— N  OC2H5        N     rather     C2H4O       N 

Hence  the  solution  of  diazonium  carbonate, 

(C6H5N2)2C03, 

cannot  give  phenol  as  one  would  expect,  if  its  diazonium 
salt  undergoes  a  direct  decomposition  analogous  to  that 
found  in  the  case  of  ammonium  carbonate. 

2.  By  the  formation  of  internal  anhydrids. — The  syn- 
diazo compounds  (like  the  maleinoid  hydrocarbon 
derivatives) ,  are  alone  capable  of  giving  in  certain  cases 
internal  anhydrids,  which  are  substances  of  cyclic 
structure,  formed  with  the  elimination  of  water.  These 
anhydrids  are  often  so  stable  that  the  substances  from 
which  they  are  derived  are  not  known. 

/N=N  /H,v 

C.H/  \  ~        C6H  /    ^N 

OH  XX 

Diazophenol. 


180  ELEMENTS   OP  STEREOCHEMISTRY 

COOR-CH2.N  COOR— CH— N 

11 
HO-N 

Diazoacetic  ester. 

Besides  the  characteristic  reactions  of  diazo  compounds, 
these  substances  possess  the  properties  to  cyclic  com- 
pounds, to  which  they  are  closely  related. 

Diazonium  derivatives  are  also  capable  of  giving,  in 
certain  cases,  internal  salts  of  the  diazonium  type. 
Thus,  diazo  sulfanilic  and  diazo  anthranilic  acids  are,  in 
in  this  respect,  closely  related  to  betain. 

(CH3)2 

/NX=N  .N, 

C.H/        >0  CH/        >0 

XSO/  XCO/ 

Diazonium  sulfanilate.  Betain. 

3.  By  relations  with  the  azo  coloring -matters. — It  is  an 
-experimental  fact,  that  of  the  two  stereoisomeric  com- 
pounds, the  syn  compound  always  reacts  much  more 
easily  (even  exclusively),  with  phenols  to  form  dyes. 
This  reaction  which  is  so  often  used  for  technical  pur- 
poses in  the  manufacture  of  coloring- matters  is  exceed- 
ingly important  from  a  stereochemical  point  of  view, 
since  it  furnishes  a  means  of  determining  the  configuration 
of  diazo  compounds. 

The  diazonium  salts  appear  at  first  to  be  capable  of 
acting  directly  with  phenols.  Here  again,  it  is  probable 
that  this  reaction  is  preceded  by  the  transformation  of 
the  salt  into  a  syndiazo  hydrate. 

It  is  found  lastly  that  the  syn  isomer  is  decomposed 
much  more  easily  than  the  anti  derivative.  Thus,  the 
syndiazo  sulfonates  are  often  decomposed  with  explosive 
violence ;  the  antidiazo  isomers  are  completely  stable. 


GEOMETRICAL   ISOMERISM  l8l 

d.  Reciprocal  transformation  of  stereoisomeric    diazo 
compounds. — Substances  which  exhibit  geometrical  isom- 
erism  possess  the  characteristic  property  of  being  trans- 
formed  easily  into  one  another.     This  behavior  which 
has  been   frequently   observed   in  the  case  of  ethylene 
derivatives,  and  particularly  well  marked  also  in  the  case 
of  oximes,  is  also  exhibited  to  a  marked  degree  in  the 
stereoisomeric  diazo  compounds,  with  this  difference,  that 
the  transformation  of  a  syndiazo  compound  into  the  anti- 
diazo   up  till   now,   alone,  has  appeared  possible.     The 
alkaline  salts  of  the  syn  series  pass  more  or  less  easily 
into  the   anti  type.     With  the    syndiazosulfonates   this 
transformation  is  effected  in  aqueous  solution  ;  with  the 
syndiazocyanids  in  alcoholic  solution.    In  the  latter  case 
it  has  often  been  observed  to  take  place  without  the  use 
of  the  solvent. 

e.  Configuration  of  diazo  compounds  of  which  there  are 
no   stereoisomers.— It  has  been  found,  in  the  series  of 
oximes,  that  two  geometrical  isomers  are  not  always  to 
be    isolated,   and  this  happens  more  frequently  in  the 
study   of   diazo  compounds.     Up  till  the  present,  one  of 
these  isomers  is  lacking  in  the  following  groups:  The 
diazo  esters,    R.N:N.OCH3;  the  thiodiazo  esters;  diazo- 
amido    compounds,    RN:N.NHR  ;    and   diazo   sulfones, 
R.N:N.SO2C6H5.     The     compounds    isolated    in    these 
groups  should  all  belong  to  the  stable  anti  type.     The 
syn    compounds  are    decomposed    spontaneously,    as  is 
the   case   when    one  tries   to  introduce    a   hydrocarbon 
group  by  treating  the  silver  salt  of  normal  diazobenzene 
with   an   alkyl   halogen   derivative,    or  are  transformed 
spontaneously  into  their   isomers,  as  has  been  proved  in 
preparing  the  diazosulfones  of  diazonium  chlorid,  or  of 


1 82  ELEMENTS   OF  STEREOCHEMISTRY 

benzenesulfonic  acid.  In  the  case  of  the  diazoamido 
compounds,  the  tautomeric  phenomena, 

R'.N:N.N.HR"  ^  R.NH.N:NR", 

exhibit  a  different  behavior  to  that  which  is  observed  in 
the  anti  series.  They  correspond  precisely  to  the  tauto- 
meric character  of  the  antidiazo  hydrates  and  the 
nitrosamins, 

R— N  R— N— H 

II  ~  I 

N— OH  N=O 

R'— N  R'— N— H 

N— NR"H  N=NR" 

f.    Influence    of   constitution   on  configuration. — The 

influence  of  constitution  on  the  configuration  of  the 
diazo  compounds  has  never  been  doubted,  but  it  has  not 
been  so  well  studied  as  has  been  the  case  in  the  series  of 
oximes.  The  alkaline  salts  of  syndiazo  benzene  appear 
to  be  more  easily  transformed  into  antidiazo  compounds, 
when  the  negative  substituents  are  more  numerous  than 
the  benzene  rest.  The  potassium  salt  of  syndiazo  ben- 
zene undergoes  this  transformation  below  100°;  thepara- 
brom  derivative  at  ordinary  temperature  and  the  para- 
nitro  derivative  almost  spontaneously.  Conversely  the 
presence  of  halogen  atoms  retard  the  transformation  of 
syn  sulfonates  into  anti  sulfonates. 

The  manner  in  which  the  haloid  salts  of  diazo  com- 
pounds, C6H5N2(Cl.Br.I),  behave  is  particularly  char- 
acteristic. They  do  not,  strictly  speaking,  exist  in  two 
isomeric  formations,  but  they  give  two  series  of  double 
salts  which  are  perfectly  distinct.  The  first  are  colorless, 
even  when  the  salt  entering  into  their  composition  is 
colorless;  e.g.,  the  double  salt  of  diazonium  and  mer- 


GEOMETRICAL   ISOMERISM  183 

cury,  C6H5N2ClHgCl.  The  others  possess  intense  color 
as  do  azo  compounds  ;  they  are  less  stable  and  are  decom- 
posed easily  into  halogen  derivatives  of  benzene,  in  the 
same  manner  as  the  syndiazo  cyanid  of  benzene,  which  is 
colored,  is  transformed  into  benzonitrile.  As  typical 
examples  may  be  mentioned  the  compounds  formed  with 
cuprous  chlorid  or  bromid,  C6H5N2Br.Cu2Br2.  It  is  very 
probable  that  the  halogen  diazonium  compound  can  exist 
in  two[isomeric  forms  (not  stereoisomeric) ;  viz.,  chlorid 
of  diazonium  and  syndiazo  chlorid  and  bromid, 

Mercuric  diazonium  chlorid,       CfiH. — N — Cl 

III 

N 

Syndiazo  cuprous  bromid,     C6H5 — N 

HCu2Br2 
Br— N 

It  is  likely  that  the  more  simple  diazo  halogen  com- 
pounds, R.N2(Cl.Br.I),  belong  to  the  syndiazo  or 
diazonium  type,  according  to  the  nature  of  the  hydro- 
carbon radical,  and  of  the  halogen. 

2.  Stereoisomeric  Azo  Compounds. 

There  are  no  stereoisomeric  compounds  of  the  azo- 
benzene  or  azo  color  series  known.  For  the  present, 
the  diazocyanids  which  are  characterized  by  the  group, 
C-j-N=N — C,  can  be  considered  as  stereoisomeric  azo 
derivatives.  All  their  members,  for  example,  the  sub- 
stances, C6H5.N=NCONH2,  belong  to  the  anti  series. 
One  may,  hence,  conclude  that  the  azo  compounds  as 
actually  known,  belong  to' the  same  series. 


THE  STEREOCHEMICAL  ISOMERISM  OF  INORGANIC 
COMPOUNDS 

BY  A.  WERNER 

In  order  to  facilitate  the  study  of  stereochemical 
isomerism  which  is  exhibited  in  certain  cases  of  inorganic 
compounds,  it  will  be  necessary  to  give  a  short  resume 
of  the  constitution  of  compounds  which  are  to  be 
mentioned  in  the  following  note.  The  substances  which 
will  be  studied  are  molecular  compounds,  of  which  the 
constitution  can  only  be  expressed  with  difficulty  by 
using  the  idea  of  valence,  unless  one  has  recourse  to 
several  secondary  hypotheses,  each  being  used  for  a 
special  case,  and  hence  being  limited  to  a  small  number 
of  compounds. 

The  constitution  of  molecular  compounds  can  be 
established  by  making  use  of  the  relations  between 
molecular  compounds  known  under  the  name  of  metallic 
ammonium  compounds,  and  double  salts,  such  as  the 
chlorids,  fluorids,  and  double  nitriles.  In  reality,  the 
two  extreme  groups  can  be  closely  connected  by  a 
certain  number  of  intermediate  substances  of  mixed 
character,  thus  establishing  a  continuous  series  in  which 
the  molecular  compounds  of  the  first  class  are  gradually 
transformed  into  double  salts. 

This  curious  transformation  will  be  taken  up  in  one  of 
the  more  simple  cases.  In  the  study  of  the  compounds 
in  question,  the  fact  that  certain  electronegative  radicals 
form  part  of  the  molecule,  and  behave  in  a  special  and 
anomalous  manner,  is  of  great  importance.  In  order  to 
explain  this  apparent  anomaly,  a  special  case  will  be 
taken. 


WERNER'S  THEORY  185 

There  are  two  ammoniacal  compounds  of  cobalt  known. 
The  first  corresponds  to  the  formula,  CO(NH3)6C13,  the 
second  to  Co  (  N  H3  )  5C13.  These  two  compound  differs  only 
by  a  .single  molecule  of  ammonia,  while  their  chemical 
properties  are  different  and  are  characterized  by  the  fol- 
lowing reactions  :  If  a  solution  of  silver  nitrate  act  upon 
the  first  salt,  three  atoms  of  chlorin  are  precipitated 
as  silver  chlorid,  and  a  nitrate,  Co(NH3)6(NO3)3,  is 
formed.  In  treating  the  second  salt  in  the  same  way, 
silver  nitrate  precipitates  but  two  atoms  of  chlorin  ;  the 
third  differs  evidently  in  its  chemical  behavior  from  the 
other  two.  There  is  thus  formed  a  chlornitrate  of  the 

Cl 
following  composition:   Co(NH3)5  /  ^Q  \  .      This   differ- 


ence is  also  observed  in  using  other  reagents  ;  thus,  by 
using  concentrated  sulfuric  acid,  the  first  salt  gives  up 
three  atoms  of  chlorin  to  form  hydrochloric  acid,  while 
the  second,  under  the  same  conditions,  loses  but  two 
molecules  of  hydrochloric  acid. 

The  three  atoms  of  chlorin  in  the  second  compound 
of  salts  have  hence  different  chemical  properties.  The 
one  of  them  behaves  in  a  special  manner  as  does  chlorin 
in  certain  organic  compounds.  Arrhenius'  hypothesis 
of  the  electrolytic  dissociation  of  salts  takes  this  anomaly 
into  account.  The  two  atoms  of  chlorin  which  have  the 
same  properties  as  chlorin  in  ordinary  chlorids,  behave 
as  ions,  while  the  third  is  deprived  of  "this  character. 

It  is  well  known  that  one  of  the  factors  which  enter 
into  the  molecular  conductivity  of  a  saline  solution  is  the 
number  of  ions  which  it  contains.  Hence  the  properties 

XNH3)6  /(NH8)6 

of  the  two  salts,   CoS  and    Co<^  ,  should 

XC13  XC13 

allow  one  to   predict   a   characteristic   difference   in  the 


l86  ELEMENTS   OF  STEREOCHEMISTRY 

molecular  conductivity  of  solution  of  these  compounds. 
Experimental  evidence  has  confirmed  this  statement,  for 
in  a  dilution  of  1000  liters  the  molecular  conductivity  of 
the  first  salt  is  equal  to  432.6  and  in  the  second  to  261.3. 

There  can  hence  be  no  doubt  that  the  first  salt  contains 
three  atoms  of  chlorin  with  identical  properties,  all  of 
which  behave  as  ions,  while  the  second  salt  contains  but 
two  having  this  property. 

The  principal  question  which  is  of  interest,  is  to  know 
what  is  the  constitutional  difference  which  will  explain 
the  different  properties  of  negative  groups  taking  part  in 
molecular  complexes  such  as  those  we  have  mentioned. 

All  chemists  are  occupied  with  this  question.  Whatever 
may  be  the  theory  adduced  as  to  the  composition  of  am- 
moniacal  metallic  compounds,  they  regard  this  difference 
as  a  consequence  of  the  different  union  of  the  negative 
group  to  the  metallic  atom  and  believe  that  this  union 
may  be  direct  or  indirect.  If  the  union  be  a  direct  one, 
that  is  to  say,  if  the  negative  group  be  directly  connected 
with  the  metallic  group,  it  does  not  behave  as  an  ion;  if 
on  the  other  hand  there  be  indirect  union,  that  is  to  say, 
if  the  negative  group  is  united  indirectly  to  the  metallic 
atom  with  the  intervention  of  molecules  of  ammonia, 
the  group  comports  itself  as  an  ion.  The  difference 
between  these  two  methods  of  union  is  indicated  bv  the 


:°\ 

XNH,C1 


following  formula:   C( 

NNHS. 

Although  this  method  of  regarding  the  constitution  of 
this  compound  does  not  coincide  very  well  with  the  idea 
which  one  usually  has  of  the  state  of  salts  in  solution,  it 
is  so  well  confirmed  by  the  experimental  facts  observed 
in  the  class  of  ammonio-metallic  compounds,  that  there 
is  scarcely  room  to  doubt  it  is  correct,  and  it  will  be 


WERNER'S  THEORY  187 

adopted  in  the  development  of  the  subject.  One  of  the 
more  simple  series  of  compounds  related  to  the  ammonio- 
metallic  salts  with  double  ions  is  that  of  the  derivatives 
of  a  divalent  platinum  atom  Pt  with  four  molecules  of 
ammonia  to  form  a  compound  of  the  formula,  Pt(NH3)4X, 
the  letter  X  representing  a  monovalent  acid  radical.  The 
reactions  of  these  salts  and  their  molecular  conductivity 
prove  that  the  two  acid  groups  behave  as  ions.  They 
represent  the  acid  radical  of  a  salt  of  which  the  positive 
part  is  the  radical,  Pt(NH8)4. 

The    second   member   of  the   series   is   a   compound, 


Pt(NH3)3X2.  The  constitutional  formula, 


NH3NH3X 


NH3X 


previously  given  does  not  correspond  with  the  observed 
molecular  conductivity,  according  to  which  one,  and  one 
only  of  the  chlorin  atoms  behaves  as  an  ion.  The  con- 
stitutional formula  should  then  be  represented  by  the 

symbol,  (Ft  x    3Mx.     The  third  member  of  the  series, 

Pt(NH3)2X,  is  found  in  two  isomeric  forms;  ztf>.,the 
salts  of  platosamin  and  the  salts  of  platosemidiamin. 
The  formulae  given  by  Cleve  and  Jorgensen  to  these 
salts  are  the  following  : 

/NH3C1  /NH3NH3C1 

Pt<  and  Pt< 

XNH3C1  >C1 

Neither  of  these  formulae  takes  into  account  the 
chemical  properties  and  the  conductivity  in  solution  of 
the  salts.  In  reality  these  substances  do  not  behave 
any  longer  as  salts  of  strong  bases,  but  rather  as  salts  in 

which    the    chlorin  (e.g.  in  the  salts  Pt  >«      3'2)  would 
V  y1*         / 

have  analogous  properties  with  those  of  this  element  in 


1  88  ELEMENTS   OF  SEREOCHEMISTRY 

the  organic  chloriii  compounds  ;  they  tend  to  become 
non-electrolytes,  and  chemical  reactions  are  very  difficult 
of  production.  All  this  would  indicate  a  formula  such  as 

•\r 

in  which  the  two  negative  radicals  should  be  in 


direct  combination  with  platinum.  In  this  case  the 
molecules  of  ammonia  should  also  be  united  in  a  corre- 
sponding way,  and  the  structural  formula  would  then  be 


3  ,  the  negative  groups  being  united  by  means 

\ 

XC1 

of  valence  as  the  term  is  habitually  employed  and  the 
molecules  of  ammonia  by  means  of  secondary  force. 
This  difference  may  be  indicated  by  saying  that  the 
molecules  of  ammonia  are  coordinated,  that  is  to  say,  that 
they  should  be  directly  linked  to  the  metallic  platinum 
atom,  although  their  union  could  not  be  due  to  that 
which  is  usually  expressed  as  valence. 

The  next  term  of  the   series  is  a  compound, 

PtNH3Cl2ClR, 

where  R  figures  as  a  monovalent  positive  group.  This 
is  a  double  salt  in  the  ordinary  sense  of  the  word. 
When  R  represents  an  atom  of  potassium,  one  obtains  a 

/NH3  -f  KC1 
general  formula  of  the  following  kind:  Pt< 

XC12 

These  bodies  do  not  behave  in  any  way  as  this  formula 
would  indicate  ;  their  molecular  conductivity  shows  on  the 

contrary  that  they  contain  a  complex  radical 

which  behaves  as  a  negative  ion,  the  potassium  being  the 
ion  with  the  electropositive  character.  The  compound 
in  question  is  a  salt  of  a  special  kind,  of  which  the  acid 


WERNER'S  THEORY  189 

radical  is  the  group  (Ptpj    3J  and   potassium  takes   the 

place  of  the  basic  radical. 

The  last  member  of  the  series  is  the  compound, 
PtCl2-f2KCl,  the  addition  product  which  is  formed  with 
platinum  chlorid  and  potassium  chlorid.  This  compound 
has  not  the  properties  which  the  formula  indicates  ;  the 
conductivity  shows  in  a  striking  manner  that  one  is  deal- 
ing with  a  salt  in  which  the  acid  radical  is  formed  by  the 
group,  PtCl4,  the  basic  radical  being  the  two  atoms  of 
potassium.  The  negative  is  PtCl4,  and  the  positive  ions 
are  K2.  Hence,  the  rational  formula  of  this  compound  is 
the  following  :  (PtCl4)K2.  To  sum  up,  these  compounds 
form  the  following  series  : 


Pt(NH3)4Cl2;     pt'3    Cl; 

[Ptcif3]K;ptC1<K*- 

In  this  series  it  is  clear  that  all  compounds  contain  a 
special  radical,  PtA4,  of  which  the  character  varies  with  the 
nature  of  the  group  A.  In  the  first  members,  the  radical 
has  basic  properties  ;  in  the  center  members  it  behaves  as 
neutral,  and  in  the  last  members  it  is  of  distinctly  acid 
character.  The  constitution  of  the  radical,  PtA4,  is  a 
matter  of  considerable  interest.  All  the  facts  known 
tend  to  show,  as  has  been  seen,  that  the  four  groups  A 
are  directly  united  to  the  platinum  atom.  If  the  four 
radicals  are  distributed  in  the  same  plane  as  the  atom  of 
platinum,  the  constitutional  formula  of  these  radicals  will 
be  represented  by 

A       A 


190  ELEMENTS   OF   STEREOCHEMISTRY 

In  assuming  a  plane  arrangement  of  the  groups,  we 
obtain  in  the  case  where  two  of  the  radicals  A  are  differ- 
ent from  the  other  two,  two  geometrical  isomers,  ex- 
pressed by  the  formulae, 


v        /A!  Av 

>Pt<  and  > 

X  / 


Pt 
A 

It  is  to  these  theoretical  formulae  that  certain  of  the 
cases  of  isomerism  which  have  been  observed  in  the  com- 
pounds of  platinum  are  related. 

One  of  the  most  characteristic  examples  is  the  isomer- 

/x, 

ism  of  the  salts  of   platosemidiamin,  Pt<^  ,  with 

XNH,), 

xX2 

the  salts  of  platosamin,   PtC  ;  the    two  series  of 

XNH,), 

compounds  correspond  to  the  same  formula, 

(NH8)2 

and  one  cannot  explain  their  isomerism  in  any  way  than 
by  means  of  stereochemical  formulae, 

NH3  Xv        /NH3 

and 


x       /3 
>Pt< 
X/        \NH3  NH/ 


One  can  even  determine  the  figures  representing  the  two 
series  of  compounds. 

If  it  be  assumed,  for  example,  that  the  first  formula 
corresponds  to  the  compounds  of  platosemidiamin,  and 
the  second  formula  to  the  platosamin  derivatives, 

Ck         /NH3         Cl     v         /NH3 
>Pt<  \Pt<          , 

CK       XNH3        NH,/      \C1 

Platosemidiamin  chlorid.  Platosamin  chlorid. 


WERNER'S  THEORY  191 

the   corresponding   compounds   which  are   formed  from 
platinum  chlorid  with  pyridin  would  have  the  formulae: 
Civ          ,Py         CK  Py 


CK  Py         Cy/  C1 

When  chlorid  of  platosemidiamin  is  treated  with 
pyridin  and  the  chlorid  of  platosemidipyridin  is  treated 
with  ammonia,  the  same  compound, 

/(NH3) 
lPt\ 

XPy2 

is  obtained.  This  compound  will  be  designated  as  the  a 
compound  and  is  formed  in  the  following  way  : 

Ck        yNH3  Py,        yNH3      1 

\pt<        +  Py,=      >P<       cij 

CK       XNH3  Py/       XNH3       I 

Ck        /Py  NH3X        ,Py 

\Pt<       +(NH8)1=          >Pt<     C12 
CK        \Py  NH/       \Py 

Similarly      by     treating     platosamin      chlorid      with 
pyridin    and    platopyridin    chlorid    with    ammonia,    a 

r      (NH,), 
compound,     Pt  C12,  is  obtained  differing  from  a, 

py, 

and  which  will  be  called  the  ft  compound.    This  latter  is 
the  stereochemical  isomer  of  the  first  .^ 
It  is  formed  in  the  following  way  : 


Ul      v           /JNJ 

xpt\ 

NH/       XC1 

CK           ,Py 

>P<       -f 
Py/       \C1 

^               rFy  \ 
-H  py2             ) 

NH/ 
-  (NH3)2                 "S\ 

Lpy      / 

/JNllg-. 

P<           C12 

\Py 

y-Py 

>P<           C12 
XNH3J       , 

192  ELEMENTS   OF   STEREOCHEMISTRY 

On  heating  the  a-  and  /^-compounds,  they  are  trans- 
formed with  a  loss  of  ammonia  and  of  pyridin  into  sub- 
stances belonging  to  the  platosamin  series,  that  is  to  say, 
into  substances  corresponding  to  the  general  formula, 

A\      /A 
>Pt< 

A/       \X 

In  considering  the  formulae  of  the  a-  and  ft-  compounds, 
it  will  be  easily  understood  how  such  a  transformation 
is  effected  ,  for  the  ^-compounds  by  loss  of  a  molecule  of 
ammonia,  and  of  a  molecule  of  pyridin,  according  to  the 
equation, 

Py  NH3         NH3,  Cl 


NH/        ^Py  Py  CK  Py 

The  compound  should  hence  furnish  a  substance  of  the 
formula, 

Py 

Ft  NH3  . 
C12 

The  /^-compound,  on  the  other  hand,  should  undergo  a 
rearrangement  into  salts  of  the  platosamin  series  in  two 
different  ways,  either  by  the  loss  of  two  molecures  of 
ammonia  or  of  two  molecules  of  pyridin,  as  follows  : 

r    Py,       /NH  Civ  NH 

>Pt<  Cl2  =  Py2  +  Vt 

LNH  \P  NH 


r     Plv        /NH  Py,        /Cl 

Vt/  C12=(NH3)2+        >Pt< 

LNH/       \Py  CK        XPy 

On  heating  the   /S-compound,   a  mixture  of  two  sub- 
stances should   be  obtained,   one  corresponding  to  the 


WERNER'S  THEORY  193 

NH8,        /Cl  Py,  Cl 


formula,  /^K  >  an^  second  to          / 

CK        XNH3  CK 

These  reactions  which  are  the  result  of  the  examination 
of  stereochemical  formulae  of  the  platosamin  and  plato- 
semidiamin  compounds,  have  in  reality  been  observed  in 
heating  these  two  compounds,  thus  furnishing  a  proof  of 
the  constitution  of  these  substances. 

It  can  be  shown  by  the  following  consideration  that 
one  would  obtain  theoretical  deductions,  which  would  not 
be  any  more  with  experimental  evidence  if  the  formulae, 

A\      /X 

/PK       ,  should  be   given  to  the  salts  of  platosamin, 

A/      \X 

X\      /X 

and  that  of       /^\.       to  tne  sa^ts  °f  platosemidiamin. 

A.  A. 

Experimentally  on  adding  to  the  salts  of  platosamin, 
Ok        XNH3  Civ        /Py 

>Pt<  and  \Pt/       , 

CK        \NH3  CK        \Py 

to  the  first,  two  molecules  of  pyridin,  and  to  the  second, 
two  molecules  of  ammonia,  one  should  obtain  a  compound, 


r3V        , 

><    Ici2, 

LNH/       XPyJ 

but  the  latter  would  be  transformed  in  three  different 
ways  into  salts  of  the  platosamin  series.  First,  by  loss 
of  two  molecules  of  ammonia,  second,  by  loss  of  two 
molecules  of  pyridin,  and  third,  by  loss  of  a  molecule  of 
ammonia,  and  a  molecule  of  pyridin. 

Hence  one   should   obtain  a  mixture  of  the  following 

Py 
three  substances  :  Pt  ^  ;  Pt  ^H^^  •  and  Pt  NH3.     This 

x2       x2  X2 

13 


194  ELEMENTS   OF   STEREOCHEMISTRY 

has,  however,  not  been  observed  even  when  the  amin  radi- 

ai 
cals  of  the  composition  Pt  b2  are  closely  related  to  one  an- 

X2 

other,  e.g.  ,  ethylamin  and  propylamin.    The  two  isomeric 
series  should  then  correspond  to  the  following  formulae  : 

x       A  x       A 


X/         A  A  X 

Salts  of  platosemidiamin.  Salts  of  platosamin. 

The  number  of  stereoisomeric  derivatives  of  divalent 
platinum  is  already  considerable.  Special  interest  is 
attached  to  the  compounds  with  sulfurous  acid  which 
have  the  formulae, 

Ck         /NH3  CL         /NH3 

>Pt<;  and  >Pt< 

HSO/       XNH3  NH/      XSO3H 

and  also  to  the  compounds, 

HSCU         /NH3  HS03\        /NH3 

>Pt<  and  >Pt< 

HSO/      XNH3  NH3  /      XHSO3 

The  compounds  so  far  investigated  have  contained  a 
complex  radical  MA4.  There  exists,  however,  a  large 
number  of  inorganic  compounds,  in  which  the  moiecule 
is  characterized  by  the  presence  of  a  complex  radical, 
MA6,  and  which  may  be  brought  together  in  a  series 
having  analogies  with  those  which  we  have  found  above 
in  the  divalent  platinum  series. 

In  order  to  give  some  idea  of  this  series  the  following 
are  formulae  of  compounds  derived  from  tetravalent 
platinum  and  divalent  cobalt  . 

Pt(NH3)6Cl4; 


WERNER'S  THEORY  195 

[Pt§H3)J  C1 ;    Pt?NH3)2 ;    [PtNHs]  K  ;   (PtC1°)K>  J 
[Co(NH3)JCl3;      [Cof^Jci,;      [cogjg J  Cl ; 

rCo(No2)3i  .     rCo(N0^OK-     rco(N0^^K  • 

LL°(NH3)J  '         L      (NH3)J  K '         |>     NH3   J  K> ' 
[Co(N02)6]K3. 

Similarly  to  that  which  was  found  with  the  radicals 
MA4  in  which  the  four  groups  are  directly  united  to  the 
metallic  atom  ;  in  these  compounds  with  the  complex 
radical,  MA6,  these  groups  are  in  direct  union  with  the 
metal.  Proof  of  this  is  given  by  the  quantitative 
examination  of  the  molecular  conductivity  of  these  sub- 
stances in  solution.  It  is  now  necessary  to  obtain  some 
idea  of  the  configuration  of  the  group,  MA6.  The  most 
simple  hypothesis  which  can  be  formed  assumes  an  octa- 
hedral arrangement,  the  metallic  atom  occupying  the 
center  of  an  octahedron,  and  the  six  groups  A  would  be 
arranged  at  the  summits  of  the  figure.  Hence,  in  a 
molecular  arrangement  of  this  sort,  one  should  obtain 
certain  cases  of  stereoisomerism,  of  which  but  one  can  be 
considered  at  present,  and  this  one  is  supported  by  experi- 
mental evidence.  Suppose  in  the  first  place,  a  radical, 
MA6,  in  which  the  four  groups  A  are  alike,  and  the  two 
others  different.  One  should  then  have  an  arrangement, 

|MA;     .   In  this  case,  the  two  radicals  A  could  occupy 

different  positions.  They  could  be  arranged  on  the  two 
summits  of  the  octahedron  which  are  bound  by  an  axis, 
or  on  two  united  by  an  edge  as  the  following  figures  will 
show  : 


196  ELEMENTS  OF  STEREOCHEMISTRY 

A 


Fig.  22. 


That  is  to  say,  the  compounds  containing  a  radical 
I  M  .  ^      should  be  obtained  in  twro  isomeric  forms. 

The  radical     M  .  f      is  found  in  certain    ammoniacal 

derivatives  of  cobalt  ;  viz.,   in  the  salts  of  praseocobalt- 
amin  corresponding  to  the  general  formula, 


(NH3 


X. 


If  the  theoretical  considerations  are  well  founded, 
these  salts  should  be  obtained  under  special  isomeric 
forms.  As  a  matter  of  fact  this  has  been  experimentally 
realized.  The  beautiful-  work  of  Jorgensen  has  shown 
that  there  exist  two  series  of  salts  of  the  formula, 

X. 

The  two  series  scarcely  differ  in  a  chemical  point  of 
view.  Of  the  three  acid  radicals  one  alone  behaves  as  an 
ion,  but  the  two  series  of  salts  are  markedly  distin- 
guished by  the  characteristic  property ;  viz. ,  that  while  the 
salts  of  the  praseocobalt  series  are  green,  the  isomeric 
purpureocobaltamin  salts  are  violet  as  their  name  would 
indicate. 


WERNER'S  THEORY 


197 


Fig.  23. 


This  interesting  case  of  isomerism  is  the  first  proof  in 
favor     of    stereochemical    isomerism    of    the   radicals, 

M  . 2   .       In  another   series,    also,    cobalt    presents  a 

special  isomerism.  It  has  been  known  fpr_ some  time 
that  there  exists  a  group  of  cobaltamin  salts  known  as 
the  derivatives  of  the  croceocobaltamin  of  the  formula, 

I  *(  NH f  \'  anc^  hence  containing  a  radical  of  the  type 

I  ^A*  '  Recently  Jorgensen  has  discovered  a  new 
series  of  compounds  having  the  same  formula, 
I  ^°( NH  f  J  '  anc^  on*y  Differing  from  the  former  in  its 

physical  properties.  The  name  flaveocobaltamin  has 
been  given  to  this  series  of  salts,  and  there  is  scarcely 
any  doubt  that  the  isomerism  of  these  two  series  is  due  to 
the  presence  of  two  isomeric  radicals  corresponding  to  the 

formula  P°/|ra  )  '  According  to  the  position  occu- 
pied by  the  two  groups,  NO2,  one  may  have  the  following 
formulae  : 


198  ELEMENTS  OF  STEREOCHEMISTRY 


Fig.  24. 

Among  the  ammoniacal  derivatives  of  tetravalent 
platinum,  there  is  found  a  case  of  isomerism  perfectly 
analogous  to  those  observed  in  the  compounds  of  cobalt. 
There  are  two  series  of  compounds  known,  corresponding 

to  the  general  formula,  Pt*v       2-     These  are  the  salts 

*H 
of    platinosemidiamin,     and    the    salts   of  platinamin ; 

here  also  the  radical    M  /,  ,4     is  present.     It  cannot  be 

doubted  that  this  again  is  a  case  of  isomerism  due  to  the 
same  cause  as  that  of  the  cobalt  compounds,  as  the  follow- 
ing formulae  represent  : 


Fig.  25. 


WERNER'S  THEORY 


Fig.  26. 


One  can  even  determine  with  a  certain  amount  of 
probability  the  spatial  formulae  corresponding  to  the  one, 
and  to  the  other  of  the  two  series.  The  compounds  of 
the  platinosemidiamin  series  and  of  the  platinamin  series 
are  formed  by  the  addition  of  two  negative  groups  to 
salts  of  platosemidiamin  and  platosamin,  the  divalent 
platinum  being  transformed  into  tetravalent  platinum. 

In  the  case  of  the  divalent  platinum  compounds,  plane 
formulae  have  been  used  and  for  salts  of  tetravalent 
octahedral  formulae.  The  most  simple  hypothesis  which 
can  be  used  with  this  connection  consists  in  assuming 
that  the  negative  groups  are  added  to  the  salts  of  divalent 
platinum  in  such  a  way  as  to  occupy  two  summits, 
united  by  an  axis  determined  by  the  four  radicals  which 
complete  the  molecule. 

This  transformation  is  explained  by  the  above  formulae 
which  give  at  the  same  time  stereochemical  formulae  for 
the  two  isomeric  series. 

In  the  short  sketch  which  has  been  given  above  of  the 
stereoisomerism  of  certain  classes  of  inorganic  com- 
pounds, some  of  the  principal  points  of  the  new  theory 
have  been  explained.  This  theory  seems  to  afford  the 


200 


ELEMENTS   OF  STEREOCHEMISTRY 


most  simple  and  satisfactory  method  of  explaining  these 
cases  of  isomerism. 

Bibliography. — A.  Werner:    "  Beitrag  zur  Konstitution    anor- 
ganischer  Verbindungen,"  Ztschr.  anorg.  Chem.,  3,  267. 
Werner  and  Miolati :  Ztschr.  phys.  Chem.,  12,  35  ;  13,  506. 


INDEX  OF  SUBJECTS. 


Accumulation         .        .          79 
Acetylene   .        .        .        .128 
compounds,  trans- 
formation of      .      98 
Acid,  acetylene  dicarboxylic  112 
aldoxime  carboxylic .  " 

145,  147 

allomucic  ...  37 
amidomaleic  .  112 
anilidomaleic  .  .112 
angelic  .  .  93,  107,  113 
aspartic  .  .  .  46 
behenoleic  .  .  99 
brassidic  .  .  99,  106 
bromcitraconic  .  97 
chlorcrotonic  .  93,  99 
chlorsuccinic  .  114 
cinnamic  ...  93 
cisdicarboxylic  .  131 
citraconic  .  .  93 

diacetyl  tartaric  .  71 
diazosulfonic  .  173,  175 
dicarboxyoxy  .  125 
dichlormaleic  .  .  97 
diethylsuccinic  .  56,  118 
dihydrophthalic  .  136 
dimethyl  dioxyglutaric  50 
elaidinic  ...  93 
erucic  .  .93,  99,  106 
fumaric  .  .  93,  114 
galactonic,  configura- 
tion ...  68 
gluconic  ...  56 
glutaminic  .  .  45 
glutaric  .  .  51,  52 
gly eerie  .  .  23,  40 


Acid,  glyoxime  dicarboxylic  152 
hexahydrophthalic  .  132 
hydrocyanic  .  .  139 


hydroxamic 
isocinnamic  . 
isocrotonic 
isosaccharic  . 
ketoximic  . 


150 
93 
93 
37 

147 


ketoxime  carboxylic  147 
lactic  .  .  20,  38,  40 
lactocar  boxy  lie  .  125 
levulinic  .  .  121 
maleic  ...  93 
maleinoid  .  .  131 
malic  .  .  20,  48 
mannonic  .  54,  56,  62 
mannosaccharic  .  27 
mesaconic  .  .  93,  117 
mucic  .  .  37,  65 
oleic  ...  93 
orthonitrophenylgly- 

oxylic  .  .  .169 
oximidocarboxylic  140 
oximidosuccinic  .  165 
phenylglycolic 

.     20,  23,  24,  40,    46 
phenylketoximepropi- 

oiiic  .  .  .  149 
phenylpropiolic  .  112 
pimelinic  ...  35 
phthalic  .  .  4 

racemic  .  34,  40,  44 
rhamnohexonic  .  66,  67 
saccharic  .  20,  37,  59,  60 
synphenylketoximeace- 

tic  -        .        .         .    149 


202 


INDEX   OF   SUBJECTS 


Acid,  talomucic,  configura- 
tion of        .        .          68 
talonic        ...      68 
tartaric  .          3,  20,  23,  34 
tetrolic       .         .         .    100 
tiglic      .        .  93,  107,  113 
trichloracetylacrylic        96 
trioxyglutaric    .         .      58 
tropic    .        .        .          42 
Adonite       ....      58 
Aldoximes      .        .        \        145 
Alloisomerism  .        .      94 

Ammonium  sodium  race- 
mate  .  .  .  .  43,  44 
Ammonium  compounds  .  83 
Amphiglyoxime  .  .  151 
Amyl  alcohol  .  .  20,  40,  46 
Amylene  ...  23 
Amyl  iodid  ...  25 
Anhydrids,  internal  .  179 
Antialdoximes  .  .  .  145 
Antidiazo  .  .  .  175 
Arabinose  .  .  .  37,  54,  5$ 
Arabite-  ....  58 

Asparagin  .  .  .  20,  23,  43 
Asymmetry  .  .  u,  18,  71 
Atropin  .  .  -36 

Axial  symmetric  formulae  90 
Azo  compounds  140,  180,  183 
Beckmann's  reaction  .  148 
Benzaldioxime  .  .  143 
Benzaldoxime  .  .  143 
Benzene  diazonium  chlorid  179 
Benzophenonoxime  .  154 
Betain  .  .  .  .  176 
Borneol  .  .  .  .  35,  52 
Camphor  .  .  .  .21 
Carbon  asymmetric  .  13 

Catalysis  .  .  .  .in 
Chlorhydrins  .  .  .  124 


Cinchonin  .  .  .  .42 
Cis  and  cistrans  .  .  90 
Cleavage  .  .  .39,  40,  42 
Cobalt,  salts  of  .  185 

Compensation  .  .  .  135 
Contact  action  .  .  155 
Conicin  .  .  .21,  23,  42 
Configuration,  advantageous 

.  89,  103 
determination 

of      .         .56 
dulcite      .  68 

galactonic  acid  68 
galactose       .      68 
mucic  acid          65 
talomucic  acid    65 
talonic  acid  .      68 
talose        .          68 
Conicin       ....      42 
Croceocobaltamin  .         .         197 
Crotonylene        ...      99 
Cryoscopy       .         .         .          81 
Cyclic  compounds    96,  122,  125 
Diazins        .        .        .        .139 
Diazo  compounds  .         140,  172 
decomposi- 
tion of     177 

Diazoamido  compounds  .  182 
Diazonium  .  .  .  174 
Diazoacetic  ester  .  .  180 
Diazonium  cyanids  .  174 
Diazohydrates  .  .  .172 
Diazonium  ^salts  .  .  183 
Diazosulfones  .  .  .  181 
Diethyl  methyl  methane  23 
Dimethyl  ethyl  methane  .  23 
Dioximes  .  .  .  151 
Diphenylglycols  .  .52 
Diphenylglyoximes  .  152 
Dulcite,  configuration  of  .  68 


INDEX   OF   SUBJECTS 


203 


Electrical  conductivity  .  120 
Ethyl  amyl  ...  20 
Bthylene  chlorid  .  .  26 

derivatives  .         .      91 
derivatives,  trans- 
formation of     .    loo 
Bthylidene  anilins          .         171 
Flaveo  cobaltamin      .        ".'    197 
Fructose,    configuration    of    61 
Furfuran         ...  97 

Galactose  .  .  .  38,  57 
configuration  of  68 
Galose  ....  38 
Geometric  isomers  .  .  92 
Glucoheptose,  configuration 

of         ....          64 
Glucose       ...        20,  57 
configuration  of  .  61 

Gulose,  configuration  of  .  61 
Glyoximes  .  .  .  151 
Heat  of  combustion  .  109,  127 
Hexachlorhexane  .  .  25 
Hydrates  in  solution  .  .81 
Hydrazones  .  140,  168,  170 
Hyoscyamins  .  .  140 

Idose  .  .^  .  .  .38 
Imido  compounds  .  .  140 
Independence  of  optical 

effect  of  atoms         .         .      79 
Influence  of  constitution        160 
Isoconicin       ...          84 
Isodiazobenzene  hydrate    .    173 
Isomers,  nature  and  num- 
ber 27 
Isomerism,  geometric     .          86 
optical      .         .        5 
Isooximes        .         .         .         172 

"K" 167 

/3-Ketoximes  .  .  .  147 
Lactams  .  .  .  .124 


Lactones  .  .  .  45,  122 
Leucin  .  .  .  20,  46 
Loss  of  activity  .  .  45 
Mannite  .  ...  .20 
Man  nose  .  .  .  38,  61 
Maximum  rotation  .  .  76 
Menthol  .  .  .  55 
Metaldehyde  .  .  .138 
Methyldiethylamyl  ammo- 
nium chlorid  .  .  84 
Methyl  isopropyl  hexamethy- 

lene         .        .        .        .    130 
Mobile  union          .        .16,  119 
Models        ....      31 
Monobrompseudobutylene     107 
Multirotation      ...      82 
Nitroantidiazobenzene     hy- 
drate   ....        178 
Nitrogen,     geometric     iso- 
mers of    .  142 
stereochemistry    4,  82 
Nitroisodiazobenzene      hy- 
drate  ....         172 
Nitrosamins        .         .         .172 
Optical  isomerism  .        5,  u,  14 
Organism,  action  of        .          40 
Oscillation           .         .         -47 
Oxazol     .         .         .         .         165 
Oximes        .         .         .         .140 
Oxyacids         .         .         .         124 
Paraamidophenol         .         .      97 
Paradioxyhexamethylene       130 
Paraformaldehyde      .         .138 
Paraldehyde    .         .         .         138 
Penicillium  glaucum          40,  41 
Pentites      ....      57 
Pentoses          ...          37 
Phenol,  oxidation  of  .         -96 
methyl  ketoxime      162 
tolylketone        .         149 


204 


INDEX  OF  SUBJECTS 


Physical  isomers 
/S-Picolin 
Picryl  hydrazin  . 
Piperazones    . 


3 

22 

141 
137 


Plane  symmetric  formulae  90 
Platinamin,  salts  of  .  198 
PI  atopy  ridin,  salts  of  -191 
Platosemidiamin,  salts  of  187 
Platosemidipy ridin,  salts  of  191 
Platosamin,  salts  of  .  187 
Polymerization  ...  82 
Polymethylene  isomers  130,  134 
Praseocobaltamin,  salts  of  196 
Projection  formulae  .  31 
Propylene  oxid  .  .  .21 
Purpureocobaltamin,  salts 

of  .  .  .  .  196 
Pyridin  .  .  .  .139 
Pyrrhol  ....  97 

Quinin  ....  42 
Quinonoximes  .  .  152 
Racemization  .  .  25,  44 
spontaneous .  48 
Rhamnose  ...  66 
Ribose  .  .  .  37,  58 
Rotatory  power  .  .  71 

Saccharomyces  ellipsoideus    41 
Saturated  compounds,  stereo- 
chemistry of    .        .        .118 


Separation,  spontaneous  43 
Stereoisomerism,  classifica- 
tion of  ...  5 
Styrol  ....  22 
Synaldoximes  .  .  145 
Syndiazo  .  .  .  .175 
Synoxazolones  .  .  159 
Synoximidoketones  .  .159 
Synthesis  of  racemic  com- 
pounds .  .  .38,  50 
Talose,  configuration  of  .  68 
Tension  theory  .  .  126 
Tetrahydro  /3-naphthalin  .  42 
Thienylglyoxylic  oxime  158 
Thiophene  aldoxime  .  165 
Tolane  dibromid 

.  93,  102,  103,  no 
Transformation,  molecular  55 
Trimethyl  isobutyl  ammo- 
nium chlorid  ...  84 
Trithioaldehydes  .  .  137 
Trithiomethylene  .  .  137 
Ty rosin  .  .  .  .  20, 46 
Unsaturated  compounds  .  91 
Valence  of  nitrogen  .  139 
Valerates  .  .  .80 

Xylite     ....          58 
Xylose        ....      37 


INDEX  OF  AUTHORS. 


Atigeli  ....  153 
Anschiitz  .  .  30,  45,  in,  171 
Arrhenius  .  .  .  120 
Auwers  .  .  56,  120,  143 
Baeyer  .  .  4,  126,  131 

Bamberger  .  .  .172 
Baumann  .  .  .41,  137 
Be"champ  ....  72 
Beckmann  ...  56 

Behrend  .  ...  .83 
Berthelot  .  .  .  44,  45 

Biltz 171 

Biot         ....  71 

Bischoff       .... 

•  51,  56,  93,  120,  121,  122,  137 
Blomstrand  and  Brlenmeyer  1 73 
Bouveault  .  .  .  21 

Bredt  .         .         .  21,    35 

Biichner  ...  131 
Carius  ....  96 
Chabrie  .  .  .  41 

Cleve  and  Jorgensen  187 

Conrad  and  Gutzheit  .  131 
Colson  ....  82 
Cnmi-Brown  ...  72 
Curie  ....  43 
Dobner  ....  96 
Dubrunfant  ...  72 
Evans  ....  124 
Fehrlin  and  Krause  .  168 
Fischer  /4,  3$,  37,38,41,  45 
1  55,  56,  58,  61,  65 
Fittig  ....  96 
Frankland  and  McGregor  .  74 
Friedel  .  .  .  129,  138 
Friedlaender  .  .  31 


Friedreich       .         .         .         100 

Goldschmidt  and  Freundt  .      78 

Guye       ...       4,  22,    72 

and  Jordan         .         .      78 

and  Rossi       .        .          81 

Hantzsch     .... 

83,  106,  139,  142,  143,  168,  173 
Jorgensen  .  .  .  196 
Kekule"  25,  35,  36,  96,  101,  in 
Korner  ....  43 
Ladenburg  .  .  .  42,  85 
L,ebel  2,  38,  77,  83,  92,  101 

Lewkowitzsch  .  .  40,  129 
Marchlewsky  .  .  44 
Michael  ....  94 
Miller  and  Plochl  .  .  171 
Ostwald  .  .  44,  80 

Pasteur  .  .  .  .  3,  43 
Pechmann  .  .  .  .173 
Petrie  ....  in 
Pictet  and  Freundler  74,  75 
Proost  .  .  .  .  136 
Ramsay  and  Shields  .  .  82 
Raoult  ....  44 
Schardinger  ...  41 
Schraube  and  Schmidt  .  172 
Schryver  and  Collie  .  .  84 
Skraup  .  .  .  .  in 
Smith  .  .  .  .162 
Stohmann  .  .  109,  127 
Tiemann  ....  37 
Tollens  .  .  .  .  72 
van  't  Hoff  2,  45,  46,  80,  94 
Walden  .  .  25,  48,  78 
Wallach  .  .  45,  54 

Welt   .         .         .         .         .79 


206 


INDEX   OF   AUTHORS 


Werner   ....  Wunderlich 

4,  47,  79,  83,  115,  129,  184  Wyrouboff 

Willgerodt          .        .         .141  Zelinsky     . 

Wislicenus      .        ...  Zincke    . 
•     3,  5i,  94,  ioo,  107,  113 


.    129 

•  45,    81 
I2i,  141 


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